Abstract
Background:
Offloading is the cornerstone of treatment of plantar diabetic foot ulcers. It limits mobility with consequent psychological and cardiovascular side effects, and if devices are removed, healing is delayed.
Methods:
We developed three non-removable techniques with increasing offloading potential (multilayer felt sole, felt-fiberglass sole, or total contact casts with ventral windows) and sensors built within. Smartwatch and web apps displayed pressure, temperature, humidity, and steps. They alerted patients, staff, and a telemedicine center when pressure limits (125 kPa) were exceeded. Patients were advised to walk as much as they had done before the ulcer episode. To evaluate the potential of this intervention, we enrolled 20 ambulatory patients in a randomized clinical trial. The control group used the same offloading and monitoring system, but neither patients nor therapists received any information or warnings.
Results:
Three patients withdrew consent. The median time to healing of ulcers was significantly shorter in the intervention group compared with controls, 40.5 (95% confidence interval [CI] = 28-not applicable [NA]) versus 266.0 (95% CI = 179-NA) days (P = .037), and increasing ulcer area was observed less frequently during study visits (7.9% vs 29.7%, P = .033). A reduction of wound area by 50% was reached at a median of 10.2 (95% CI = 7.25-NA) versus 19.1 (95% CI = 13.36-NA) days (P = .2). Participants walked an average of 1875 (SD = 1590) steps per day in intervention group and 1806 (SD = 1391) in the control group.
Conclusions:
Sensor-assisted wound therapy may allow rapid closure of plantar foot ulcers while maintaining patient’s mobility during ulcer therapy.
Keywords
Introduction
Diabetic foot syndrome (DFS) is a common, devastating, and costly consequence of diabetes. 1 Approximately one in four people with diabetes will develop a foot ulcer in their lifetime. Amputations are a frequent consequence occurring in about 10% of active diabetic foot episodes. An active diabetic foot ulcer (DFU) takes an average of six months to become inactive. In the subsequent years, ulcers recur at a rate of about 30% per year, making the diabetic foot a lifelong condition. 2 The loss of pain-induced signaling to change behavior is the central aspect of the disease and has many consequences. 3 Affected people do not limit their physical stress in response to high-pressure loads and may suffer unnoticed trauma with each step. Once ulcers are present, they are frequently not perceived as detrimental to health, and action is taken late despite prior education. Caring for these patients thus means relying less on their personal responsibility and more on outside support than for other conditions related to diabetes.
Offloading is the cornerstone 4 of therapy for most DFUs and is difficult to achieve in neuropathic patients. Insufficient offloading 5 often leads to the recommendation to offload the entire foot, 6 which severely restricts mobility, often for months. Limited mobility is considered detrimental to cardiovascular fitness, 7 which may contribute to the high mortality of people with DFS. 8 The restriction of mobility negatively affects independence and quality of life and may increase the risk of developing depression. Mobility is not part of the selection criteria to recommend offloading devices in evidence-based guidelines, maybe because published evidence focuses on ulcer closure and amputation. 4 Data on the association between offloading techniques and premature death are lacking. From a holistic perspective, by integrating the preservation of mobility with the protection of ulcerated regions, health care professionals can assist people with diabetes in maintaining their functional abilities, mitigating the risk of additional complications, and enhancing their overall long-term outcomes.
Sensors have been used by several groups in the prevention of foot ulcers9-19; however, their potential use in monitoring ulcers differs in several aspects. In the management of active ulcers, the point of interest is well defined, the surveillance period is limited to the duration of the ulcer, the potential benefits related to duration of surveillance are higher, and patients might better appreciate the benefits of adherence to therapies if they have better and more immediate feedback from electronic devices.
The aim of this study was to examine the impact of sensor-assisted wound therapy (SAWT) on the healing of DFUs. This study is, to the best of our knowledge, the first published use of SAWT in the treatment of active DFUs. In addition, we explored whether the graduated use of personalized devices could enable mobility.
Methods
In a randomized, controlled, multicenter feasibility trial evaluating two parallel groups, the control group used the same system as the treatment group, but neither patients nor therapists received information or alerts. Permuted block randomization was used in sequentially numbered blocs of four people in two strata based on the severity of the lesion. Randomization took place at the University of Applied Science in Krefeld and was communicated to the study centers via telephone call.
The trial was registered (DRKS-ID: DRKS00023094) and approved by the ethical committee of the medical association of Northern Rhineland.
Two outpatient centers, one outpatient clinic and one private practice, both situated in the north of Cologne/Germany in a working-class suburb, recruited consecutive patients aged 18 to 85 with diabetic plantar foot ulcers. If necessary, peripheral arterial disease (PAD) was corrected and the ulcer surgically debrided prior to randomization. Patients were excluded if they had active Charcot neuroarthropathy or if they did not agree to be contactable by phone during the study period. The primary endpoint was the time to 50% ulcer area reduction. Secondary endpoints included reduction of between-visit intervals (14 days), showing increased ulcer surface, time to absolute ulcer healing, proportion of patients with ulcers healed within three months, pain, quality of life, and economic benefits.
Statistical calculations were done in RStudio (Version 2023.06.0, 2023 Posit Software, Boston, USA), R version 4.3.0 (2023-04-21 ucrt), packages tableone version 0.13.2 for baseline characteristics and ggplot2 version 3.4.2 for Kaplan-Meier curves.
Special attention was paid to the offloading technique as part of the complex intervention (Figure 1) and developed in advance. We standardized custom-made, non-removable offloading devices to allow three grades of immobilization: (1) multilayer felt applied in a defined manner under the foot 2 (Fi-mobile) without any immobilization, (2) a stiff sole combining felt and fiberglass 20 (FiF!-mobile Figure 1c) to immobilize metatarso-phalangeal (MTP) joints, 21 or (3) a ventral windowed total contact cast (VW-TCC) 22 to immobilize MTP joints and ankle joints. The devices allow walking, can be produced immediately by the wound care team, are not removed by the patients, and allow access to wound care and dressing changes. These techniques aim to offload the ulcer completely. The choice was made by the clinical investigator based mainly on size, location, and depth. Their effectivity was tested during the initial fitting trying to trigger alarms when walking 100 m and descending 10 flights of stairs. If alarms occurred, the offloading had to be adjusted or the technique had to be replaced with a more effective one.
(a) Electronics and (b) housing of the small and flexible sensor unit. (c) Fif!-mobile device integrating the sensor unit, visible at the base of the cutout, and its use. (d) Patients wear an offloading device integrating the sensor unit. They also wear a smartwatch receiving and displaying data from the sensor unit and possibly alarms. Via mobile Internet, sensor data are sent to the iFoot database and are displayed together with medical data concerning the diabetic foot ulcer. The database application may send alarms to the diabetic foot clinic and to the telemedicine center. Staff at the clinic or at the telemedicine center may communicate with the patient about the findings and what might be the case to do.
A sensor unit (Figure 1a and b) was integrated in the devices. It monitored pressure, temperature, and humidity. It was connected via Bluetooth to a smartwatch (Galaxy Watch Active2 LTE, Samsung Electronics) running the iFoot app. Transmission occurred every 10 minutes. Pressure was recorded as peak pressure on the sensor area of 15.7 mm2. When pressure exceeded 125 kPa, the sensor unit made an additional connection to the smartwatch and displayed an audible and visual alarm. Patients could turn off the alarm and start a dressing change mode without alarms for 30 minutes. The watch sent measurements, number of steps, events, and actions to the server via mobile Internet. If alarms were not properly responded to, the server sent emails informing the therapeutic team and a telemedicine center, ensuring that all alarms had timely consequences. An algorithm decided to inform the team by email if the patient did not quit the alarm or had three or more alarms in one hour. The email contained a link to check when it was read. If there was no response within two hours, another email was sent to the telemedicine center with a similar link to check for a response. The email client on the responsible doctor’s smartphone generated an alert sound when an email arrived from the i-foot server.
The server also provided a web interface with wound documentation and sensor data. The server, apps, and sensor unit (Figure 1d) were developed as part of the project.
Offloading techniques and sensor integration in the devices did not differ between groups. Patients were advised to walk as much as they did before the DFU episode. Patients and therapeutic teams of the control group were unable to see the results of the sensor measurements and did not receive alarms.
At the end of the study, several patients did not achieve ulcer healing and continued to receive treatment based on the best standard care practices until full ulcer closure. The date of ulcer healing during this follow-up period of 7.5 months was used to calculate the corresponding secondary endpoint.
To calculate the number of steps per day, we calculated an average number of steps per day of each patient as individual average. Days with missing data before 10
To calculate the number of patients required to achieve a power of 80% at an alpha level of 0.05, we assumed a median time to bisection of the wound area of three months in the control group and 1.15 months in the intervention group. Based on these assumptions, a total of 40 patients would have had to be recruited, with 20 patients equally divided between the two groups.
In reporting on this study, we followed the CONSORT guidelines. 23
Results
Twenty people participated in the study (12 intervention, 8 control). The first participant was randomized on February 22, 2021, and the last on September 9, 2021, and treated until October 15, 2021. Follow-up of the unhealed ulcers was until June 30, 2022. Three participants were excluded because they did not use the system within the first two weeks (2 intervention, 1 control) and withdrew consents (Figure 2).
Flowchart of the profile of the study.
All 10 ulcers of the intervention group healed within the study period and received the intervention until healing was complete. Four of the seven ulcers in the control group closed within the study period, two further ulcers healed during follow-up of 7.5 months, and one remained unhealed. Most patients used FiF!-mobil soles (four intervention, five control) or a TCC (five intervention, two control). One patient’s ulcer was offloaded using felt alone (intervention).
Baseline data of the patients can be found in Table 1. Deterioration occurred in 14 of 75 intervals between visits, significantly less in the intervention group (3/38 vs 11/37, P = .033 Pearson’s chi-square test with Yates’ continuity correction).
Baseline Characteristics of Patients in Treatment and Control Groups.
Abbreviations: BMI, body mass index; MTH, metatarsal head; TCC, total contact cast; HbA1c, glycosylated haemoglobin; IPJ, interphalangeal joint; SINBAD-score, Site, Ischemia, Neuropathy, Bacterial Infection, and Depth.24
The median time to 50% ulcer area reduction was shorter in the intervention group compared with controls (10.2 vs 19.1 days, 95% confidence interval = 13.36-NA vs 7.25-NA, log-rank test P = .2; Figure 3a). No ulcer in the control group healed within 90 days, but 7 out of 10 in the intervention group healed (P = .017 Pearson’s chi-square test with Yates’ continuity correction for between group comparison). The median time to complete healing of ulcers was shorter in the intervention versus control patients (40.5 vs 266.0 days, 95% confidence interval = 179-NA vs 28-NA, log-rank P = .037; Figure 3b).
Probability of healing by (a) 50% or (b) complete over time.
Patients experienced an average of 1.54 alarms/day. Three of them were contacted by the telemedicine center due to alarms in five cases, and one patient took initiative and contacted the therapeutic team. Three patients were seen between scheduled visits to resolve offloading issues. Patients in control groups did not perceive any problem with insufficient offloading.
The individual average of steps per day varied from 305 to 4812 (mean = 1851, SD = 1462). There was no difference between groups (intervention 1875; SD 1590; control 1806; SD 1391).
Before starting the therapy, four patients had “some pain” or “considerable pain,” which then disappeared. During the study, two patients in the control group had “severe pain” or “moderate pain” while the surface of their ulcers increased. Overall, pain was never a persistent problem (events: one intervention, four control).
Discussion
Sensor control shortened the time to healing of plantar DFUs. Four predefined endpoints related to duration of ulcer therapy: time to 50% ulcer area reduction, time to ulcer healing, proportion of patients with ulcers healed within three months, and reduction of between-visit intervals (14 days) showing increased ulcer surface. All showed improvement related to SAWT.
We observed four types of situations in which pressure sensors (Figure 4) had an impact on time to ulcer healing: First, the sensors helped to recognize inadequate offloading during the 14-day interval between study visits (Figure 4g). The number of intervals with deterioration was significantly lower in the intervention group.
Treatment and sensor readings of a 57-year-old blue-collar worker with an ulcer of 2.04 cm2 located beneath the fifth MTH. (a) Ulcer at the beginning of sensor-assisted wound therapy. (b) Offloading as standardized for ulcers at the fifth MTH. (c) Second study visit after four weeks. According to the patient, the ulcer closed one week before this visit. (d) Steps per day ranging from approximately 1000 to 4800. (e) Temperature measurements. During the dressing change, the sensor was placed on a radiator. (f) Humidity was 100% during most of the time. (g) Pressure readings. The vertical lines are the maximum pressure values in an interval of 10 minutes; green if below the threshold of 125 kPa; red if above.
Second, sensors warned of incomplete offloading during the initial fitting. In some cases, the type of offloading was changed from felt alone to Fif!-mobile during this first visit. No such changes were made at subsequent visits or in the control group.
Third, two patients reported that they had changed their walking habits to limit the alarms. One patient with a heel ulcer loaded the forefoot more than before to avoid triggering alarms. The other patient with an ulcer on the first metatarsal head (MTH) changed her habit of walking up stairs.
Finally, sensors warned of insufficient offloading after a dressing change, usually because the dressing unintentionally filled the necessary gap between the ulcer and the supporting surface. Effects 2 to 4 were not foreseen at the time the study was designed and were only reported anecdotally.
Average steps per day (Figure 4d) varied inter- and intra-individually. One patient was dependent on nursing staff before the onset of the DFU and walked 211 to 399 steps per day. All other patients walked more corresponding to an independent living. The most active patient walked 2299 to 8183 steps per day.
Mobility is important for an independent living and a good quality of life. Patients do not like being limited in the numbers of steps. 25 This study demonstrates that SAWT enhances techniques that offload ulcer and immobilize joints in the ulcer area, without limiting the number of steps and therefore improving patient’s quality of life.
Humidity (Figure 4f) and temperature (Figure 4e) can be used to determine whether the device was removed or not. We did not notice patterns of removal except for dressing changes. We did not notice correlations between temperature or humidity and wound closure.
In general, the technique was perceived in a positive light by patients and staff members. Further studies are planned to formally assess the effect of SAWT on workload and working conditions as well as patient’s emotional response to this therapy. The limitations concern mainly the low number of participants due to the fact that the study took place during the COVID-19 pandemic. One of the two centers, which is the outpatient clinic of a hospital, could enroll only one patient. The benefit was great enough to reach significant results in most of the predefined endpoints concerning the speed of ulcer closure. Another limitation is the predefined requirement to complete the PRO-questionnaires without the help of the staff. Many patients were not able to do so or left many questions without answer. For this reason, we were unable to determine depression or satisfaction with the therapy without bias. As a third limitation, due to the limited battery life of the smartwatch, we only calculated the average of steps for 12 patients who had at least two days with minimal data transmission (last transmission after 10
No serious adverse events were attributed to the therapy.
Conclusions
In conclusion, SAWT may combine unrestricted mobility with accelerated closure of DFUs, addressing at the same time cardiovascular fitness, quality of life, and health of the feet. This could be seen as a major progress in DFU therapy.
Footnotes
Abbreviations
DFS, diabetic foot syndrome; DFU, diabetic foot ulcer; DM, diabetes mellitus; HCP, health care professional; NA, not applicable = infinity in survival analysis; TCC, total contact cast; VW-TCC, ventral windowed total contact cast.
Ethical Approval
This study was approved by the ethics committee of the North Rhine Medical Chamber (application no. 0001297).
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was funded by the EU (European Regional Development Fund ERDF), the Federal State of North Rhine-Westphalia (NRW).