One Step at a Time
One of the biggest health problems in the world is also one of the most solvable. Yet, millions of people continue to be afflicted every year, spend time in hospitals for costly treatment, and, in many cases, become permanently disabled when one of their limbs has to be amputated (see “The Diabetic Foot Epidemic”). Some motivated medical, engineering, and other professionals, however, envision a better future where new collaboration-inspired technologies address this devastating problem: foot ulcers among people who have diabetes.
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How big a scourge is the diabetic foot ulcer? “In the United States alone, there are between 26 and 30 million people with diabetes right now, and the most common reason that they are admitted to the hospital is not for heart attack or stroke or even high blood sugar. It is for a hole, called an ulcer, in the foot,” Armstrong says . “About half of the time, those ulcers become infected, and about 20–30% of those infections lead to some level of amputation.”
Other countries are seeing similar crises. “Around the world, there is an amputation due to diabetes every 20 seconds. It’s a worldwide epidemic,” he says. Various studies have attempted to put a dollar figure on diabetic foot ulcers. One estimated that about a third of the approximately US$116 billion in direct costs spent in the United States in 2007 on the treatment of diabetes and its complications was linked to the treatment of diabetic foot ulcers .
The immensity of the problem has been noted worldwide. The International Diabetes Federation and the World Health Organization have created an International Working Group on the Diabetic Foot. As the U.S. representative of the group, Armstrong notes that the group’s primary focus has been clinician education through its Step by Step program, which is led by Zulfiqarali Abbas, a consultant physician at Muhimbili University College of Health Sciences and Abbas Medical Centre, in Tanzania, and Vijay Viswanathan, the joint director of the M.V. Hospital for Diabetes and Diabetes Research Centre in India.
“The Step by Step program goes around the world educating physicians and surgeons and, more importantly, nurses and other technicians so that we are creating different tiers of foot specialists who are aware of the problems of the diabetic foot,” Armstrong says. He would like to see a similar educational program in the United States. “We need as many people as possible to be active in the fight against diabetic foot ulcers.”
Armstrong adds, “This is a really big problem; it’s a very complicated problem, and it represents a massive unmet need worldwide. But it is ultimately solvable. I think it is worth a life’s work.”
- D. Armstrong, “Mind the gap: Disparity between research funding and costs of care for diabetic foot ulcers,” Diab. Care, vol. 36, no. 7, pp. 1815–1817, July 2013.
- V. R. Driver, M. Fabbi, L. A. Lavery, and G. Gibbons, “The costs of diabetic foot: The economic case for the limb salvage team,” J. Am. Podiatr. Med. Assoc., vol. 11, no. 5, pp. 335–341, Sept.–Oct. 2010.
A hub for this research is the Southern Arizona Limb Salvage Alliance (SALSA), set in the University of Arizona Department of Surgery. It is an interdisciplinary effort to address the global epidemic of dangerous infections and amputations caused by diabetic foot ulcers, explained David G. Armstrong, D.P.M., M.D., Ph.D., a professor of surgery at the University of Arizona College of Medicine and codirector of SALSA with his partner, prominent vascular surgeon Joseph L. Mills Sr., M.D. Much of SALSA’s work involves drawing together physicians, engineers, surgeons, and others to bring new technologies to bear on foot ulcers.
“The reason that diabetic foot ulcers develop is that people with diabetes lose the ‘gift of pain,’” Armstrong says, referring to the phrase used by one of his mentors, the world-renowned orthopedic specialist Paul Brand (1914–2003). The condition arises because diabetics typically undergo prolonged exposure to high blood sugar. And high blood sugar, along with the narrowing of blood vessels that it can cause, ultimately affects blood flow. This can then cause nerve damage known as peripheral neuropathy, which can lead to a loss of feeling in the feet.
If a patient experiences repetitive stresses to a lower extremity from a stone in a shoe, from ill-fitting footwear, or from some other source, that patient can literally wear a hole in his or her foot and not know it. “The same vertical stresses or sheer stresses that caused that hole—that ulcer—can lead to inflammation and tissue breakdown, then infection, and in too many cases, amputation,” Armstrong says.
Nip It in the Bud
One of the best ways to prevent diabetic foot ulcers is to identify the causative stress well before an ulcer forms, and that is what SALSA researchers are doing. Spurred by Brand’s work showing that inflammation is accompanied by heat, SALSA researchers began considering how they could use that observation to prevent ulcers. “We gave patients handheld thermometric devices to check their skin temperature at focal spots on one foot and compare them with the corresponding spots on the other foot,” Armstrong says. When a patient found an area with a higher temperature, they could adjust their activity to reduce the stress to that spot. “We did three separate federally sponsored, randomized trials, and the trial results suggest very strongly that this really could help people.”
The only thing missing was an entrepreneur to take the idea and turn it into a commercial product that patients could buy and use. That entrepreneur turned out to be “some clever gentlemen from the Massachusetts Institute of Technology (MIT) and Harvard Business School,” according to Armstrong. “They gave us a call a couple of years ago, and told us that they had been reading our stuff but didn’t quite understand why the business model for the handheld devices wasn’t developed. They wanted to do something.”
From that out-of-the-blue beginning, the MIT and Harvard students formed the start-up company Podimetrics Inc., of Cambridge, Massachusetts, which has now evolved the handheld device into prototype home appliances, specifically floor mats for the bathroom or bedroom. Patients need only step on the mat for temperatures and blood flow patterns to be recorded, trends noted, and changes reported. “The mat might tell the patient, for instance, that a spot on the big toe is reading hotter than it has been for the last few weeks,” Armstrong says. Depending on how it is set up, the mat might then recommend that the patient take it easy on that foot for a while; if it’s applicable, the mat might send a reminder to the patient to use the special orthopedic, pressure-relieving shoe that the doctor ordered; or it might notify the patient’s doctor or nurse of the change in condition. “It’s like a home security system for the body,” he says.
While work on the mat continues, SALSA researchers are developing a somewhat similar technology. In this case, they are working on sensor-equipped “smart” socks as a preventive measure, says SALSA researcher Bijan Najafi, Ph.D., an associate professor of surgery and engineering at the University of Arizona and director of the Interdisciplinary Consortium on Advanced Motion Performance (iCAMP), a subsidiary SALSA research and development group (Figure 1). “The smart sock is not highly innovative from the engineering side. Rather, it is borrowing a concept that has for decades been used for other applications,” Najafi explains, noting that the socks are based on fiber optics technology that measures temperature, pressure, and joint angle (Figure 2). The latter is captured by bends in the fiber optics. The clinical evaluation of the smart socks is continuing, and Najafi’s group is working with a Chicago company to commercialize the socks for use in a medical setting.
SALSA researchers are also working with Calgary-based Orpyx Medical Technologies, Inc., on smart insoles that will measure skin temperature as well as pressure or stress and feed this information back to the patient (Figure 3). “This is a thin and really quite elegant sensory-substitution device that signals the patient in real time that there’s a problem,” Armstrong explains. The signal transmits wirelessly from the insole to a smartwatch worn by the patient. This Orpyx insole is already available in select markets in the United States and is scheduled to be released in Canada and Europe in 2014.
Virtual Exercise, Real Results
In a completely different preventive approach, iCAMP researchers are developing a technology that helps improve the blood flow to nerves in the lower extremities by encouraging patients to engage in physical activity (Figures 4 and 5). The major issue the research group is addressing is balance, according to Najafi. Once patients begin to experience decreased sensation in their feet, their balance is affected. “They develop fear of falling, so they start to limit their activity and cut out exercises because they are too difficult or may put them at risk of developing foot ulcers,” he says. This not only impacts their quality of life but also can exacerbate the neuropathies that caused the loss of feeling in the first place.
To reach these fall-leery patients, Najafi’s group is turning to virtual reality. “We use wearable sensors to give real-time feedback to patients who are using their own motion to navigate an avatar through a safe virtual environment,” he explains. “This includes a lot of signal processing, which must extract meaningful information out of these sensors and visualize it so that the patients—and their doctors—can get the right feedback to enhance patients’ mobility while minimizing the risk.”
As an example, patients use iCAMP’s virtual reality system to walk around obstacles. “This is a good exercise for these patients because it helps them to better perceive the position of the lower extremity, (a sensation that) is lost due to neuropathy,” Najafi says. During what he calls a virtual obstacle-crossing exercise, an animation of the patient’s lower extremities, based on data from body-worn sensors, is shown on the screen in real time.
“For each trial, a virtual obstacle moves toward the animation of the user at a fixed simulated speed. The objective of the task is to lift the indicated foot to avoid the approaching virtual obstacle,” Najafi explains. If the approaching obstacle is successfully avoided, the obstacle disappears and a positive feedback sound is played. If the foot is not lifted in time, the obstacle disappears with a negative feedback sound. This simple interface allows subjects to perceive motor errors, such as joint position, with respect to the obstacle. “This is a key source for motor learning and retention,” he says.
In addition, such virtual exercise reduces patient risks (e.g., of hitting a real obstacle or falling) while helping the patient gain confidence. Successes in the virtual environment give patients the confidence to navigate in a real environment. To further encourage patients, the researchers tried to make the technology fun and motivating for the patient by arranging tasks into levels of difficulty so that patients can challenge themselves to progress through the levels. “We did a trial , and found that the patients love it because it feels like a game, and, at the same time, they are seeing an average of 70% enhancement in their balance compared to a control group ,” Najafi notes. In practical terms, that improvement can mean the difference between a patient opting to go about normal daily activities rather than staying home. Najafi’s group published the proof of concept for the virtual reality technology in December  and is working with a company to commercialize it in 2015 or 2016.
This is just one example of how interactions between engineers, clinicians, and patients can tackle important problems, according to Najafi. “Sometimes, the solution is not overly complex. Sometimes it can be a simple, targeted game that can help patients enhance their quality of life.”
New Tech Coming Soon
That kind of interdisciplinary approach is also important for the imaging of diabetic foot tissues, especially for viewing blood flow in the extremities as well as surface foot tissues. Some imaging technologies, such as the LUNA system developed by the company Novadaq of Ontario, Canada, use fluorescence angiography. This system is designed to allow clinicians to view and assess tissue perfusion (blood flow to the tissue) in foot ulcers and other similar wounds so that they can provide optimal treatment on a patient-by-patient basis.
SALSA is also pursuing imaging but in an alternate form. For this project, which is a collaborative effort with optical engineers at the University of Arizona, visible and fluorescence images are captured simultaneously and then projected onto a head-mounted display, described Rongguang Liang, Ph.D., associate professor in the university’s College of Optical Sciences.
“The head-mounted display that we are developing has a large field of view and tunable image contrast based on the room light,” Liang says. “Our device will have well-registered visible and fluorescence images, which will be a great benefit for further diagnosis because visible images provide detailed tissue surface information on the diabetic foot.”
Liang’s group already has a prototype of the device and is currently continuing “to improve the imaging systems and integrate more advanced function to aid doctors in diagnosis,” he says.
Armstrong remarks, “In Liang’s group, we have an outstanding team on the optics side that is working on this device. This is early and exciting work, and it is showing great promise.”
Other technologies are also under way in labs around the world to address diabetic foot ulcers, Armstrong says. They include:
- augmenting foot tissues, perhaps through such methods as implants (similar to breast implants) that provide cushioning and make the foot less susceptible to injury
- developing so-called negative pressure wound therapy, in which a type of vacuum is applied to the wound to draw out fluid, increase blood flow to the area, and promote wound healing
- addressing wound management through cell-based or stem-cell technologies—perhaps in combination—not only to repair but also to deliver a superstructure to mend the wound
- using new approaches to stimulate angiogenesis (new blood vessel formation) in foot tissues and combat neuropathies or to modulate inflammation and amplify the natural process of healing
- fighting infection with antimicrobial topical technologies that could be derived from biologics or from animals that show some promise in mitigating local inflammation, as well as stopping infection from becoming even more widespread.
Many Disciplines Are Part of the Solution
All of these projects have one thing in common: They rely on interdisciplinary teamwork, Armstrong says. “These are medical problems, but they’re also engineering problems. We need doctors, patients, the medical device industry, and engineers working together to get out in front of this health crisis.”
This is a perfect opportunity for engineers to contribute solutions, says Jeff Goldberg, dean of the College of Engineering at the University of Arizona. He funds portions of the salaries for some of the engineers who hold SALSA faculty appointments and looks forward to providing lab space for SALSA researchers in the college’s new engineering-innovation building. “I support SALSA for a couple of reasons. First, engineers help people, and this is a great area where we can have an impact and help an awful lot of people. Second, when we have people like Dave Armstrong, who have a great vision and know that all of the different team members, from doctors to nurses to technology-transfer experts to engineers, have skills they contribute, it’s a dream opportunity.”
Najafi echoes those thoughts. “The best fruit for an engineer is to see that his or her research actually becomes a product that is used by the larger population and makes a difference in the health of our society. When I look at the Web sites of the companies we are working with on some of these technologies for diabetic foot ulcers, I’m so proud to say that yes, the research that we are doing really makes a difference.”
With a health problem as extensive as that of diabetic foot ulcers—an estimated 3 million diabetic patients undergo treatment for foot ulcers every year in the United States and Europe alone—new measures can indeed have a profound impact, and multidisciplinary efforts are the way to develop those new measures, Armstrong adds. “Diabetic foot ulcers are preventable. And by working together—doctors, engineers, patients, and all the other people who take part—we can beat this.”
- G. S. Grewal, R. Sayeed, M. Schwenk, M. Bharara, R. Menzies, T. K. Talal, D. G. Armstrong, and B. Najafi, “Balance rehabilitation: Promoting the role of virtual reality in patients with diabetic peripheral neuropathy,” J. Am. Podiatr. Med. Assoc., vol. 103, no. 6, pp. 498–507, Nov./Dec. 2013.
- B. Najafi, “Gamification of exercise and its application for fall prevention among patients with diabetes and peripheral neuropathy,” in Proc. Qatar Foundation Annu. Research Conf., 2013. [Online].
- M. Schwenk, E. DeHaven Jordan, B. Honarvararaghi, J. Mohler, D. Armstrong, and B. Najafi, “Effectiveness of foot and ankle exercise programs on reducing the risk of falling in older adults: A systematic review and meta-analysis of randomized controlled trials,” J. Am. Podiatr. Med. Assoc., vol. 103, no. 6, pp. 534–547, Nov./Dec. 2013.