Cardiovascular Engineering and Technology, Vol. 7, No. 1, March 2016 (Ó 2016) pp. 1–6 DOI: 10.1007/s13239-016-0257-y
Clinical Immersion and Biomedical Engineering Design Education: ‘‘Engineering Grand Rounds’’ MATTHEW WALKER III and ANDRE´ L. CHURCHWELL Vanderbilt University, Nashville, TN, USA (Received 22 January 2016; accepted 28 January 2016; published online 8 February 2016) Associate Editor Ajit P. Yoganathan oversaw the review of this article.
pid design opportunities to solve real-life/time problems and to work in near and present cross-functional teams in an environment that leverages the close physical and intellectual proximity of the Vanderbilt Schools of Medicine and Engineering. On Saturday mornings, a time often reserved for clinical case presentations, the clinician presents a patient-based problem that may have a BME device/process solution to the senior BME design students with an open innovation and interactive format. Once the problem is richly delineated, the students utilize their problem observation and problem identification skills to analyze the patient, and problem in this open intellectual forum. The senior design students then formulate the relevant needs-screening and assessment and cycle back to the clinician about potential solution sets in the form of a novel device description or process within 24–48 h. The 1-h sessions may invoke design/development opportunities for learning that include all components of BME innovation from ideation and concept/conflict mapping to product/process incubation in the form of a written proposal back to the clinicians.
Abstract—Grand Rounds is a ritual of medical education and inpatient care comprised of presenting the medical problems and treatment of a patient to an audience of physicians, residents, and medical students. Traditionally, the patient would be in attendance for the presentation and would answer questions. Grand Rounds has evolved considerably over the years with most sessions being didactic—rarely having a patient present (although, in some instances, an actor will portray the patient). Other members of the team, such as nurses, nurse practitioners, and biomedical engineers, are not traditionally involved in the formal teaching process. In this study we examine the rapid ideation in a clinical setting to forge a system of cross talk between engineers and physicians as a steady state at the praxis of ideation and implementation. Keywords—Innovation, Grand rounds, Engineering, Design, Ideation.
INTRODUCTION Our efforts at Vanderbilt University in the Schools of Engineering and Medicine have created an experience for students that scaffold biomedical engineers and student engineers into the process of clinical immersion and Biomedical Engineering (BME) device, process and systems design. This program provides opportunities for clinicians to ‘‘offload’’ some of their engineeringrelated clinical problems to senior BME design students in a way that gives the students an early and important blur of the lines that separate the practice of engineering and medicine. This concept presents a new format for design courses, although well-embedded in our faculty-level collaborations. The goal is to provide the undergraduate students with systems-thinking and ra-
METHODS Under traditional BME education, graduate students work in a close and coordinated environment with clinicians as part of their Masters or their PhD research. We feel that senior students interacting with clinicians in such a fresh, intellectually-stimulating process will develop the capstone skills of applying mathematics, science, and engineering to solve problems at the interface between BME and clinical processes (diagnosis, intervention, device therapeutics, health care delivery, drug delivery, personalized medicine, bioinformatics, imaging quantification, translational imaging, hospital efficiencies, etc.). Undergraduate BME students desire opportunities
Address correspondence to Matthew WalkerIII, Vanderbilt University, Nashville, TN, USA. Electronic mail: [email protected]
1 1869-408X/16/0300-0001/0
Ó 2016 Biomedical Engineering Society
2
WALKER
AND
CHURCHWELL
FIGURE 1. Sphere of Collaborative Innovation: A shared why for better ‘‘up take’’.
to work directly with clinical research teams. Many students assume that their undergraduate experience will allow close rich working relationships with physicians, but in most BME programs, this is not the case. The engineering grand rounds experience will serve as a platform for greater undergraduate BME inclusiveness in clinical problem solving. At its full evolution, this concept or process may lead to BME students (undergraduate and graduate) attached to a medical intensive care unit (MICU) team. Similarly, we have found that Pharm.D students and the physician team have enjoyed a greater understanding of drug interactions and new indication by working directly with clinicians in the appropriate settings.2 Patient care has been greatly enhanced by this improved scaffolding of partnership in the training of pharmacy students. A similar analogue can exist with incorporating BME undergraduate students into the MICU, CVICU (cardiovascular intensive care) and SICU (surgical intensive care) teams. These interactions can also stimulate research projects and enhance specific solutions. The practice of medicine is becoming increasingly dependent on technology4 and the earlier we build cross-discipline engineering stakeholders into the clinical thinking process, the stronger will be our complex, technology-driven ecosystems. However, often there is not the grafting of stakeholders in the early stages of the patient problem statement and hence by the time the clinician reaches out to the engineer, the problem has been circumscribed and the solutions are embedded in the needs assessment prematurely. Engineering grand rounds allows for there to be an early and appropriate push from the engineer and pull from the clinicians at the needs assessment stage. As in Fig. 1, once there is agreement between the clinician and the biomedical engineer that we share the belief in the why (identification of the problem, needs assessment and needs screening), in a common language and a common appreciation of the magnitude of
concern, each stakeholder branches out to execute on the how and the what using either medical, surgical or technological solutions. In the whole scheme of things, reflecting together to ideate around the why, is the pivotal piece that blurs boundaries and cross barriers between disciplines. The why is where there is the beginning of common culture, even though each stakeholder uses different languages and different toolboxes at the solutions stages of what and how. The Sphere of Collaborative Innovation used in EGR is a heuristic technique based on the established premise that people want to collaborate with people who believe what they believe, and hence, making that why common ground. Clinicians and biomedical engineers are exactly the same in their why (treating the patient); it is only the what and the how that is different. The biomedical engineer treats patients with a device, or process, or other approaches that characterize the what and the how. The clinicians use medicine, surgery or other approaches unique to them, that characterize their how. Hence, there is not collaboration really around the what and how, as that is where there is a functional gulf. But by crossing over the gulf, and reaching across to the why, the collaboration goes between innermost of the sphere to the outermost. Teaching with the EGR approach is our way of connecting thought leaders in engineering and medicine around the why where there is a shared operational belief even at the undergraduate level. The Participants and Key Drivers The Co-leaders of EGR are required to be those clinicians that have a key background and comfort with innovation. In choosing the approximately 2.5% of physicians population that are innovation minded in their own right to co-lead the EGR, and to have in the
Clinical Immersion and Biomedical Engineering Design Education
mix the 13.5% fast follower physician population as visionaries1 a systematic breach across the chasm results and cultural barriers are removed. These barriers conventionally have stymied the push of collaboration from the engineers, but this new EGR model has fostered an enlightening and appropriate pull from the clinicians (Fig. 1) in the early engineering design process. The platforms created will be hallmark features of medicine’s future; and an ongoing education program that embraces these notions will shorten the translational solutions relay time between fresh clinical needs identification and engineering solution. The systems level advantages include teaching and applying techniques that streamline day-to-day processes that require coordination of cross-disciplined teams of health professionals. Ultimately, the exercise will educate all involved on how co-joined thought leaders across the biomedical spectrum are able to forge a new thrust where engineers and healthcare providers advance novel approaches capable of dissecting components and needs in ways that better identify, invent, and implement biomedical technical systems, devices and processes, treatments, deliveries, and surgical intervention, for a more broad and deep clinical ecosystem of patient care. There are many additional benefits that the undergraduate BME students will derive. They will be exposed to the ethical framework that is involved in many complex medical problems.3 The exposure to this creative and instructive process will create a generation of undergraduate BME students that will be better prepared to take greater advantage of future educational opportunities, i.e., graduate or medical school. Furthermore, it will force all of us involved in BME research and education to be more proximally anchored to the patient and the humane process of solving the patient’s problem. Lastly, as we seek to promote translating their research to the bedside, this new educational format will serve to catalyze the translation process. The work conducted on vertebrate animals was approved by and performed in accordance with guidelines of the institution(s) where it was performed (e.g. Institutional Animal Use and Care Committee, IACUC), adheres to the Guide in the Care and Use of Laboratory Animals established by the U.S. National Academy of Sciences (or guidelines that insure equivalent or higher standards of care). RESULTS [CASE A]: The Teaching Paradigm and the Engineering Grand Rounds Resulting Design Project The learning environment is set up such that the BME students are presented the case study by the clinician, in the medical school setting that is separate
3
and distinct from the engineering classroom. Prior to the actual presentation, we remind the students of the design elements that go into open-innovation ideation with concept mapping governing the thinking. Identify, invent and implement are the three pillars upon which the EGR model is developed. The identify phase of design is of paramount importance in this portion of the education as it creates the opportunity for the student to be exposed to the needs finding and needs screening that is a part of the more noisy, less structured environment where problems for design are generated. In the standard design classroom approach, the problems are already well defined and circumscribed and the identification of needs have been completed in the problem. The uniqueness of this teaching approach is that the student is exposed to the ill-defined stage of problems that require observation, needs identification as the earliest most part of design. During the presentation of the clinical case, each student is encouraged to go to the white board and write out open innovation needs they attach to the patient case without any preconceived notions of what solutions are envisioned by the clinical case presenter. The sessions are highly engaging with both clinical and BME faculty present to help guide the direction of open innovation needs identification. This pedagogical tool of open innovation and needs identification, teaches the students how to brainstorm without judgment, how to leverage and build off of collegial thoughts, how to create great questions and not just converge upon the right answer in the context of real life clinical concerns. Once students have completed the EGR sessions, they submit 10 of the needs identified and screened to the clinician and then the clinicians with the BME faculty talk about concept mapping around solutions to the problems. This cycle is iterative with the students, and then the project is scoped (see below). Clinical Case Presentation and Problem Hydrophilic polymers administered shortly after nerve injury have shown to improve axonal fusion. Currently, there is only one opportunity to deliver, and that is at the time of surgery. Ideally, sustained coverage would provide greater efficacy. There has been success in both morphologically fusing the nerves together as well as improving nerve function. At the Vanderbilt Medical Center, Dr. Wesley Thayer has been able to administer polyethylene glycol (PEG), an FDA approved hydrophilic polymer, after suturing the severed nerves together with considerable success (Fig. 2). He has also observed that in cases where the antioxidant methylene blue (MB) is used before PEG, the percentage of fused axons appears to increase leading to rapid functional recovery of transected nerves in animal models.
4
WALKER
AND
CHURCHWELL
minimize systemic toxicity. This allows the distal and proximal ends of the severed neurons to fuse more readily. Our solution will be easily and quickly implementable at the time of surgery. It will enhance fine motor articulation and maximize motor function postsurgery. Our solution needs to be safe, cheap, and effective. These advancements can prevent amputations in U.S. military veterans. Design
FIGURE 2. Texas Red Dye diffused across (a) native nerve, (b) crushed nerves without PEG induced fusion, or c crushed nerves with PEG induced fusion. Dashed lines denote plane of transection. (d) Mean + SEM sciatic funtional index scores showing rat hind limb function are plotted at various times for rats with 4 conditions: nerves cut + without repair (n = 8), nerves cut + suture repair (n = 6) + suture repair + MB + PEG (n = 10), sham (no nerve injury, n = 6). Cut + suture is not significantly improved over cut (p > .50), however cut + suture + MB + PEG and Sham are significantly improved compared to cut (p < .0001 for both) via ANOVA. During the time frame measured, sham is significantly improved over cut + suture + MG + PEG (p < .0001).
Specific Problem Statement Although these techniques have shown promise, PEG and MB can only be administered in a one-dose bolus during surgery while the wound is still open. A re-administration or continuous administration of PEG and MB over a number of days is currently not possible, but may further improve clinical outcomes. Solution Dr. Thayer’s current technique calls first for the suturing of the severed nerve. The sutured repair is irrigated with a calcium free solution (Plasma-lyte AÒ). Next, 100 lM MB solution is applied to the environment to expel vesicles and decrease oxidative damage. Then, a 190 mM solution of 3.35 kDa PEG in water is applied to the repair. The PEG is added to promote membrane sealing. Finally, the repair is washed with a calcium ion containing solution (Lactated Ringers) to wash away the PEG and promote vesicle mediated sealing of any Spyder Catheter design remaining membrane injuries. A catheter-based system can apply PEG and MB to the site of nerve injury over a long period of time. A catheter system can be used to deliver PEG even after the wound is closed. Skin, bone, and muscle tissue can begin to heal, while still delivering PEG locally to
The Unifuse Catheter (Angiodynamics) is currently used to deliver thrombolytic agents to blood clots intravenously. It uses ‘‘pressure response outlets’’ to ensure even dispersion of the thrombolytic agents. Pressure response outlets are small slits cut into the body of the catheter, parallel to the body of the catheter. Several of these slits are cut into a distal portion of the Unifuse Catheter. They are arranged radially in 5 rows around the catheter. There are several rows of slits in a distal region of the catheter called the infusion region. These slits remain closed and allow no infusate to escape until a critical pressure is reached. When the critical pressure is reached, all of the slits distend simultaneously, allowing infusate to escape and be evenly distributed. The Unifuse is currently being used to deliver thrombolytic agents along the length of an intravenous blood clot. The length of a nerve injury is variable, and this technology can be used to distribute PEG and MB along the entire damaged region. A 4 French, prototype Unifuse catheter that is 90 cm in length with a 20 cm infusion pattern was shown to evenly distribute PEG in bench top testing (data not shown). The viscosity of PEG did not limit the distribution and a physician or nurse could easily deliver he force required to infuse PEG. We would like to test a smaller version of the Unifuse. Unifuse makes a 5 French catheter that is 45 cm in length, with a 5 cm infusion pattern. This would be the catheter size required for testing in a murine model. This catheter design utilizes pressure response outlets to deliver PEG and MB evenly. There were several designs that led to prototypes. The lead design was the ‘‘Spyder’’ catheter. Any catheter design with a ‘‘cuff’’ around the nerve wound is not extractable without surgery because pulling the catheter out will also destroy the nerve repair. The Spyder catheter branches into multiple spindle-like tubes, forming multiple infusion regions that later converge. This shape (Fig. 3) allowed the pressure-controlled catheter to envelope the site of injury, providing an evenly distributed flow of nerve repair solution. Each spindle of this design was able to release solution in a controlled and even manner through evenly spaced slits. The design was not be more costly than other catheters types
Clinical Immersion and Biomedical Engineering Design Education
5
through a separate incision created outside of the wound, to minimize infection. A surgical tunneler or a spear on the end of the catheter can be used for this. CONCLUSION
FIGURE 3. Diagram illustrating the Spyder Catheter design.
already on the market. This catheter design comes packaged with PEG and MB in a single package, so they can be opened and used together. It will be marketed as a ‘‘peripheral nerve repair system.’’ At the time of surgery, the nerve will be sutured and Plasmalyte A, MB, PEG, and Lactated Ringers will be applied sequentially. The catheter will be placed around the repair site and tunneled through the skin. The wound will be closed. Once per day for two weeks, Plasmalyte A, MB, PEG, and Lactated Ringers is applied to the site through the catheter. Following this regimen, a minor surgery will be performed to remove the catheter. Any catheter design will be placed following a thorough cleaning of the wound. As catheters placed in an unsterilized wound will increase the chances of infection, antibiotics will be appropriately administered. Furthermore, the catheter needs to exit the body
The preliminary design was implemented in murine models. After the initial iterative redesign process, there will be a provisional patent for the leading design. Human trials will be conducted after approval from the Institutional Review Board. The Vanderbilt Medical Center, a level I trauma center, performs about 240 peripheral nerve repairs per year. Our PI, Dr. Thayer, performs many of these. After gaining IRB approval, Phase I clinical trials will be performed on a small group of patients (10–20 patients) to provide data on the safety of the device. After safety has been demonstrated, we will apply for a full patent. We will then seek to gain 510 K clearances from the Food and Drug Administration. Phase II clinical trials will provide data on the efficacy of our design in treating peripheral nerve injuries. Funding for the Phase II trials will be sought from external sources including the Department of Defense. If an increased efficacy in clinical outcome can be shown, our system will be highly marketable to the Department of Defense. The potential is great for our system to be implemented in surgeries at military bases worldwide or following airlift to medical facilities. ENVIRONMENT
WALKER
6
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REFERENCES
CONFLICT OF INTEREST 1
The authors acknowledge no conflicts of interest and that there have been no human subjects used in these studies.
HUMAN AND ANIMAL RIGHTS AND INFORMED CONSENT A statement regarding approval and accordance appears in the ‘‘Methods’’ section of the manuscript.
Casalino, L., et al. External incentives, information technology, and organized processes to improve health care quality for patients with chronic diseases. JAMA 289(4):434–441, 2003. 2 Erstad, B. L., et al. Interdisciplinary patient care in the intensive care unit: focus on the pharmacist. Pharmacotherapy 31(2):128–137, 2011. 3 Krumholz, H. M., et al. Mortality, hospitalizations, and expenditures for the medicare population aged 65 years or older, 1999–2013. JAMA 314(4):355–365, 2015. 4 Wang, C. J., and A. T. Huang. Integrating technology into health care: what will it take? JAMA 307(6):569–570, 2012.
Clinical Immersion and Biomedical Engineering Design Education: ‘‘Engineering Grand Rounds’’ MATTHEW WALKER III and ANDRE´ L. CHURCHWELL Vanderbilt University, Nashville, TN, USA (Received 22 January 2016; accepted 28 January 2016; published online 8 February 2016) Associate Editor Ajit P. Yoganathan oversaw the review of this article.
pid design opportunities to solve real-life/time problems and to work in near and present cross-functional teams in an environment that leverages the close physical and intellectual proximity of the Vanderbilt Schools of Medicine and Engineering. On Saturday mornings, a time often reserved for clinical case presentations, the clinician presents a patient-based problem that may have a BME device/process solution to the senior BME design students with an open innovation and interactive format. Once the problem is richly delineated, the students utilize their problem observation and problem identification skills to analyze the patient, and problem in this open intellectual forum. The senior design students then formulate the relevant needs-screening and assessment and cycle back to the clinician about potential solution sets in the form of a novel device description or process within 24–48 h. The 1-h sessions may invoke design/development opportunities for learning that include all components of BME innovation from ideation and concept/conflict mapping to product/process incubation in the form of a written proposal back to the clinicians.
Abstract—Grand Rounds is a ritual of medical education and inpatient care comprised of presenting the medical problems and treatment of a patient to an audience of physicians, residents, and medical students. Traditionally, the patient would be in attendance for the presentation and would answer questions. Grand Rounds has evolved considerably over the years with most sessions being didactic—rarely having a patient present (although, in some instances, an actor will portray the patient). Other members of the team, such as nurses, nurse practitioners, and biomedical engineers, are not traditionally involved in the formal teaching process. In this study we examine the rapid ideation in a clinical setting to forge a system of cross talk between engineers and physicians as a steady state at the praxis of ideation and implementation. Keywords—Innovation, Grand rounds, Engineering, Design, Ideation.
INTRODUCTION Our efforts at Vanderbilt University in the Schools of Engineering and Medicine have created an experience for students that scaffold biomedical engineers and student engineers into the process of clinical immersion and Biomedical Engineering (BME) device, process and systems design. This program provides opportunities for clinicians to ‘‘offload’’ some of their engineeringrelated clinical problems to senior BME design students in a way that gives the students an early and important blur of the lines that separate the practice of engineering and medicine. This concept presents a new format for design courses, although well-embedded in our faculty-level collaborations. The goal is to provide the undergraduate students with systems-thinking and ra-
METHODS Under traditional BME education, graduate students work in a close and coordinated environment with clinicians as part of their Masters or their PhD research. We feel that senior students interacting with clinicians in such a fresh, intellectually-stimulating process will develop the capstone skills of applying mathematics, science, and engineering to solve problems at the interface between BME and clinical processes (diagnosis, intervention, device therapeutics, health care delivery, drug delivery, personalized medicine, bioinformatics, imaging quantification, translational imaging, hospital efficiencies, etc.). Undergraduate BME students desire opportunities
Address correspondence to Matthew WalkerIII, Vanderbilt University, Nashville, TN, USA. Electronic mail: [email protected]
1 1869-408X/16/0300-0001/0
Ó 2016 Biomedical Engineering Society
2
WALKER
AND
CHURCHWELL
FIGURE 1. Sphere of Collaborative Innovation: A shared why for better ‘‘up take’’.
to work directly with clinical research teams. Many students assume that their undergraduate experience will allow close rich working relationships with physicians, but in most BME programs, this is not the case. The engineering grand rounds experience will serve as a platform for greater undergraduate BME inclusiveness in clinical problem solving. At its full evolution, this concept or process may lead to BME students (undergraduate and graduate) attached to a medical intensive care unit (MICU) team. Similarly, we have found that Pharm.D students and the physician team have enjoyed a greater understanding of drug interactions and new indication by working directly with clinicians in the appropriate settings.2 Patient care has been greatly enhanced by this improved scaffolding of partnership in the training of pharmacy students. A similar analogue can exist with incorporating BME undergraduate students into the MICU, CVICU (cardiovascular intensive care) and SICU (surgical intensive care) teams. These interactions can also stimulate research projects and enhance specific solutions. The practice of medicine is becoming increasingly dependent on technology4 and the earlier we build cross-discipline engineering stakeholders into the clinical thinking process, the stronger will be our complex, technology-driven ecosystems. However, often there is not the grafting of stakeholders in the early stages of the patient problem statement and hence by the time the clinician reaches out to the engineer, the problem has been circumscribed and the solutions are embedded in the needs assessment prematurely. Engineering grand rounds allows for there to be an early and appropriate push from the engineer and pull from the clinicians at the needs assessment stage. As in Fig. 1, once there is agreement between the clinician and the biomedical engineer that we share the belief in the why (identification of the problem, needs assessment and needs screening), in a common language and a common appreciation of the magnitude of
concern, each stakeholder branches out to execute on the how and the what using either medical, surgical or technological solutions. In the whole scheme of things, reflecting together to ideate around the why, is the pivotal piece that blurs boundaries and cross barriers between disciplines. The why is where there is the beginning of common culture, even though each stakeholder uses different languages and different toolboxes at the solutions stages of what and how. The Sphere of Collaborative Innovation used in EGR is a heuristic technique based on the established premise that people want to collaborate with people who believe what they believe, and hence, making that why common ground. Clinicians and biomedical engineers are exactly the same in their why (treating the patient); it is only the what and the how that is different. The biomedical engineer treats patients with a device, or process, or other approaches that characterize the what and the how. The clinicians use medicine, surgery or other approaches unique to them, that characterize their how. Hence, there is not collaboration really around the what and how, as that is where there is a functional gulf. But by crossing over the gulf, and reaching across to the why, the collaboration goes between innermost of the sphere to the outermost. Teaching with the EGR approach is our way of connecting thought leaders in engineering and medicine around the why where there is a shared operational belief even at the undergraduate level. The Participants and Key Drivers The Co-leaders of EGR are required to be those clinicians that have a key background and comfort with innovation. In choosing the approximately 2.5% of physicians population that are innovation minded in their own right to co-lead the EGR, and to have in the
Clinical Immersion and Biomedical Engineering Design Education
mix the 13.5% fast follower physician population as visionaries1 a systematic breach across the chasm results and cultural barriers are removed. These barriers conventionally have stymied the push of collaboration from the engineers, but this new EGR model has fostered an enlightening and appropriate pull from the clinicians (Fig. 1) in the early engineering design process. The platforms created will be hallmark features of medicine’s future; and an ongoing education program that embraces these notions will shorten the translational solutions relay time between fresh clinical needs identification and engineering solution. The systems level advantages include teaching and applying techniques that streamline day-to-day processes that require coordination of cross-disciplined teams of health professionals. Ultimately, the exercise will educate all involved on how co-joined thought leaders across the biomedical spectrum are able to forge a new thrust where engineers and healthcare providers advance novel approaches capable of dissecting components and needs in ways that better identify, invent, and implement biomedical technical systems, devices and processes, treatments, deliveries, and surgical intervention, for a more broad and deep clinical ecosystem of patient care. There are many additional benefits that the undergraduate BME students will derive. They will be exposed to the ethical framework that is involved in many complex medical problems.3 The exposure to this creative and instructive process will create a generation of undergraduate BME students that will be better prepared to take greater advantage of future educational opportunities, i.e., graduate or medical school. Furthermore, it will force all of us involved in BME research and education to be more proximally anchored to the patient and the humane process of solving the patient’s problem. Lastly, as we seek to promote translating their research to the bedside, this new educational format will serve to catalyze the translation process. The work conducted on vertebrate animals was approved by and performed in accordance with guidelines of the institution(s) where it was performed (e.g. Institutional Animal Use and Care Committee, IACUC), adheres to the Guide in the Care and Use of Laboratory Animals established by the U.S. National Academy of Sciences (or guidelines that insure equivalent or higher standards of care). RESULTS [CASE A]: The Teaching Paradigm and the Engineering Grand Rounds Resulting Design Project The learning environment is set up such that the BME students are presented the case study by the clinician, in the medical school setting that is separate
3
and distinct from the engineering classroom. Prior to the actual presentation, we remind the students of the design elements that go into open-innovation ideation with concept mapping governing the thinking. Identify, invent and implement are the three pillars upon which the EGR model is developed. The identify phase of design is of paramount importance in this portion of the education as it creates the opportunity for the student to be exposed to the needs finding and needs screening that is a part of the more noisy, less structured environment where problems for design are generated. In the standard design classroom approach, the problems are already well defined and circumscribed and the identification of needs have been completed in the problem. The uniqueness of this teaching approach is that the student is exposed to the ill-defined stage of problems that require observation, needs identification as the earliest most part of design. During the presentation of the clinical case, each student is encouraged to go to the white board and write out open innovation needs they attach to the patient case without any preconceived notions of what solutions are envisioned by the clinical case presenter. The sessions are highly engaging with both clinical and BME faculty present to help guide the direction of open innovation needs identification. This pedagogical tool of open innovation and needs identification, teaches the students how to brainstorm without judgment, how to leverage and build off of collegial thoughts, how to create great questions and not just converge upon the right answer in the context of real life clinical concerns. Once students have completed the EGR sessions, they submit 10 of the needs identified and screened to the clinician and then the clinicians with the BME faculty talk about concept mapping around solutions to the problems. This cycle is iterative with the students, and then the project is scoped (see below). Clinical Case Presentation and Problem Hydrophilic polymers administered shortly after nerve injury have shown to improve axonal fusion. Currently, there is only one opportunity to deliver, and that is at the time of surgery. Ideally, sustained coverage would provide greater efficacy. There has been success in both morphologically fusing the nerves together as well as improving nerve function. At the Vanderbilt Medical Center, Dr. Wesley Thayer has been able to administer polyethylene glycol (PEG), an FDA approved hydrophilic polymer, after suturing the severed nerves together with considerable success (Fig. 2). He has also observed that in cases where the antioxidant methylene blue (MB) is used before PEG, the percentage of fused axons appears to increase leading to rapid functional recovery of transected nerves in animal models.
4
WALKER
AND
CHURCHWELL
minimize systemic toxicity. This allows the distal and proximal ends of the severed neurons to fuse more readily. Our solution will be easily and quickly implementable at the time of surgery. It will enhance fine motor articulation and maximize motor function postsurgery. Our solution needs to be safe, cheap, and effective. These advancements can prevent amputations in U.S. military veterans. Design
FIGURE 2. Texas Red Dye diffused across (a) native nerve, (b) crushed nerves without PEG induced fusion, or c crushed nerves with PEG induced fusion. Dashed lines denote plane of transection. (d) Mean + SEM sciatic funtional index scores showing rat hind limb function are plotted at various times for rats with 4 conditions: nerves cut + without repair (n = 8), nerves cut + suture repair (n = 6) + suture repair + MB + PEG (n = 10), sham (no nerve injury, n = 6). Cut + suture is not significantly improved over cut (p > .50), however cut + suture + MB + PEG and Sham are significantly improved compared to cut (p < .0001 for both) via ANOVA. During the time frame measured, sham is significantly improved over cut + suture + MG + PEG (p < .0001).
Specific Problem Statement Although these techniques have shown promise, PEG and MB can only be administered in a one-dose bolus during surgery while the wound is still open. A re-administration or continuous administration of PEG and MB over a number of days is currently not possible, but may further improve clinical outcomes. Solution Dr. Thayer’s current technique calls first for the suturing of the severed nerve. The sutured repair is irrigated with a calcium free solution (Plasma-lyte AÒ). Next, 100 lM MB solution is applied to the environment to expel vesicles and decrease oxidative damage. Then, a 190 mM solution of 3.35 kDa PEG in water is applied to the repair. The PEG is added to promote membrane sealing. Finally, the repair is washed with a calcium ion containing solution (Lactated Ringers) to wash away the PEG and promote vesicle mediated sealing of any Spyder Catheter design remaining membrane injuries. A catheter-based system can apply PEG and MB to the site of nerve injury over a long period of time. A catheter system can be used to deliver PEG even after the wound is closed. Skin, bone, and muscle tissue can begin to heal, while still delivering PEG locally to
The Unifuse Catheter (Angiodynamics) is currently used to deliver thrombolytic agents to blood clots intravenously. It uses ‘‘pressure response outlets’’ to ensure even dispersion of the thrombolytic agents. Pressure response outlets are small slits cut into the body of the catheter, parallel to the body of the catheter. Several of these slits are cut into a distal portion of the Unifuse Catheter. They are arranged radially in 5 rows around the catheter. There are several rows of slits in a distal region of the catheter called the infusion region. These slits remain closed and allow no infusate to escape until a critical pressure is reached. When the critical pressure is reached, all of the slits distend simultaneously, allowing infusate to escape and be evenly distributed. The Unifuse is currently being used to deliver thrombolytic agents along the length of an intravenous blood clot. The length of a nerve injury is variable, and this technology can be used to distribute PEG and MB along the entire damaged region. A 4 French, prototype Unifuse catheter that is 90 cm in length with a 20 cm infusion pattern was shown to evenly distribute PEG in bench top testing (data not shown). The viscosity of PEG did not limit the distribution and a physician or nurse could easily deliver he force required to infuse PEG. We would like to test a smaller version of the Unifuse. Unifuse makes a 5 French catheter that is 45 cm in length, with a 5 cm infusion pattern. This would be the catheter size required for testing in a murine model. This catheter design utilizes pressure response outlets to deliver PEG and MB evenly. There were several designs that led to prototypes. The lead design was the ‘‘Spyder’’ catheter. Any catheter design with a ‘‘cuff’’ around the nerve wound is not extractable without surgery because pulling the catheter out will also destroy the nerve repair. The Spyder catheter branches into multiple spindle-like tubes, forming multiple infusion regions that later converge. This shape (Fig. 3) allowed the pressure-controlled catheter to envelope the site of injury, providing an evenly distributed flow of nerve repair solution. Each spindle of this design was able to release solution in a controlled and even manner through evenly spaced slits. The design was not be more costly than other catheters types
Clinical Immersion and Biomedical Engineering Design Education
5
through a separate incision created outside of the wound, to minimize infection. A surgical tunneler or a spear on the end of the catheter can be used for this. CONCLUSION
FIGURE 3. Diagram illustrating the Spyder Catheter design.
already on the market. This catheter design comes packaged with PEG and MB in a single package, so they can be opened and used together. It will be marketed as a ‘‘peripheral nerve repair system.’’ At the time of surgery, the nerve will be sutured and Plasmalyte A, MB, PEG, and Lactated Ringers will be applied sequentially. The catheter will be placed around the repair site and tunneled through the skin. The wound will be closed. Once per day for two weeks, Plasmalyte A, MB, PEG, and Lactated Ringers is applied to the site through the catheter. Following this regimen, a minor surgery will be performed to remove the catheter. Any catheter design will be placed following a thorough cleaning of the wound. As catheters placed in an unsterilized wound will increase the chances of infection, antibiotics will be appropriately administered. Furthermore, the catheter needs to exit the body
The preliminary design was implemented in murine models. After the initial iterative redesign process, there will be a provisional patent for the leading design. Human trials will be conducted after approval from the Institutional Review Board. The Vanderbilt Medical Center, a level I trauma center, performs about 240 peripheral nerve repairs per year. Our PI, Dr. Thayer, performs many of these. After gaining IRB approval, Phase I clinical trials will be performed on a small group of patients (10–20 patients) to provide data on the safety of the device. After safety has been demonstrated, we will apply for a full patent. We will then seek to gain 510 K clearances from the Food and Drug Administration. Phase II clinical trials will provide data on the efficacy of our design in treating peripheral nerve injuries. Funding for the Phase II trials will be sought from external sources including the Department of Defense. If an increased efficacy in clinical outcome can be shown, our system will be highly marketable to the Department of Defense. The potential is great for our system to be implemented in surgeries at military bases worldwide or following airlift to medical facilities. ENVIRONMENT
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REFERENCES
CONFLICT OF INTEREST 1
The authors acknowledge no conflicts of interest and that there have been no human subjects used in these studies.
HUMAN AND ANIMAL RIGHTS AND INFORMED CONSENT A statement regarding approval and accordance appears in the ‘‘Methods’’ section of the manuscript.
Casalino, L., et al. External incentives, information technology, and organized processes to improve health care quality for patients with chronic diseases. JAMA 289(4):434–441, 2003. 2 Erstad, B. L., et al. Interdisciplinary patient care in the intensive care unit: focus on the pharmacist. Pharmacotherapy 31(2):128–137, 2011. 3 Krumholz, H. M., et al. Mortality, hospitalizations, and expenditures for the medicare population aged 65 years or older, 1999–2013. JAMA 314(4):355–365, 2015. 4 Wang, C. J., and A. T. Huang. Integrating technology into health care: what will it take? JAMA 307(6):569–570, 2012.
