نمیتوان فشار را تحمل کرد: ارتباط بین ایستادن بدون حفاظ، راه رفتن و بهبود زخم در افراد دیابتی Can’t Stand the Pressure: The Association Between Unprotected Standing, Walking, and Wound Healing in People With Diabetes

Diabetes is a global epidemic and is one of the most significant public health challenges of our day. It is estimated that 642 million people worldwide will have diabetes by 2040,1 of which about 50% will develop peripheral neuropathy (PN).2 Largely because of PN and loss of protective sensation, lower extremity complications of diabetes constitute a major public burden in both the developed and developing world and affect 15-25% of those with PN.2-5 The most common complication, the diabetic foot wound, occurs most frequently when pressure and shear (cycles of stress) are multiplied by activity (episodes of initiating movement, walking, and standing).6,7 Management of physical activity and its overall pattern including postures and weight-bearing activities in patients with diabetic foot disease is poorly understood.7-10 Clinicians are cautious about advising extra activity to their patients with diabetic foot ulcers (DFU). There is concern about excessive foot loading causing a delay with healing of DFU because of repetitive moderate stress.11,12 However, the published data regarding this association are not entirely clear. Furthermore, there are few if any data evaluating the role of prolonged low-grade pressure on healing. While walking on an unprotected wound may be plausibly detrimental to healing, the role of exercise on health benefits cannot be ignored, even in patients with DFU. Recent evidence suggests that exercise causes a trend of increased joint mobility, reduced psychological distress, and increased peripheral blood flow, which might reduce the risk of falling and contribute in accelerating wound healing.13-16 On the other hand, prolong immobilization of foot may lead to deconditioning, muscle atrophy and weakness17,18 and ultimately alter quality of life and wellbeing of patient even after successful wound healing. Thus it stands to reason to mobilize foot and encourage patients with DFU to be active and mobile. However, it is unclear whether weight-bearing activities even with protective offloading would suppress the impact of repetitive stress on plantar wound and its negative impact on success of wound healing. Several studies have explored the physical activity levels in individuals at high risk for DFU.19-23 To our knowledge, none have explored activity pattern including postures (i.e., sitting, standing, lying, walking) and locomotion characteristics (e.g., number of taken steps, unbroken walking bouts, walking speed, postural transition, etc.) in individuals with DFU. Few studies suggested that exercise activity may have positive effect on physiological (e.g., oxygen) and psychological (e.g., stress) functioning and thus could enhance rates of wound healing.15,24,25 However, none of these studies explored the effect of physical activity pattern in patients with a DFU. Thus, there are no standardized guidelines available to dose physical activity in this population and clinicians are generally concerned about excessive loading of the foot leading to poor wound healing outcomes.8 There exists only a paucity of data (more specifically evidence from a single randomized study) investigating the levels and profiles of physical activity in this population.26 Therefore, the purpose of the present study was to report the patterns of physical activity as a function of removable and irremovable offloading modality in people with DFU. Methods Forty-nine eligible subjects with confirmed diabetes and PN, age 18 or older with noninfected, non ischemic, plantar neuropathic foot ulcers were entered into this prospective randomized controlled trail. Subjects with major foot amputation, active Charcot arthropathy, ankle brachial index (ABI) of 0.5 or less,27 history of alcohol or substance abuse within 6 months, or unable to keep research appointments were excluded. If subjects had noncompressible vessels (ABI > 1.2), we measured toe pressures to determine a toe brachial index (TBI). A TBI > 0.65 was required for enrollment. In addition, we excluded those patients, who could not be accommodated in a standard removable cast walker or were unable to walk a distance of minimum 20 minutes with or without an assistive device. Subjects were recruited from 2 clinical sites including Hamad Medical Co (HMC) in Doha, Qatar and the Southern Arizona Limb Salvage Alliance (SALSA) clinic at the University of Arizona Health System, USA. The study received local institutional review board (IRB) approval from the University of Arizona and Hamad Medical Corporation. All subjects were given written informed consent before recruitment. Using a computer generated randomization list, participants were assigned to one of the two off-loading modalities; removable cast walker (RCW, DH Offloading Walker, Ossur, Reykjavik, Iceland) and instant total contact cast (iTCC, the same RCW wrapped with a cohesive bandage, rendering it irremovable; Figure 1).28,29 Sequentially numbered, opaque envelopes that contained the study group assignment were provided to each site. At the time of randomization, an envelope was opened by the study coordinator to identify the study group assignment. All subjects received standard of care including wound debridement and moisture retentive dressings by a wound care specialist. This methodology was described in previous studies.30,31 Subjects in RCW group were instructed to cleanse the wound daily and apply a dressing. They were instructed to inspect the wound at each dressing change and how to detect signs that the wound is worsening. They were asked to report these signs to the study coordinator immediately. Subjects in this group were also instructed to only walk with the RCW in place and to leave it on at all times. Subjects randomized to the iTCC group did not have daily dressing changes due to the irremovable nature of the device. Instead they received both written and oral instructions on device care, bathing, and signs of cast deterioration. On weekly basis, the iTCC was removed for the purpose of wound care and wound assessment similar to subjects in the RCW group and reapplied at the end of wound care and assessment. Outcomes including change in wound size, wound closure, and daily physical activities were assessed at baseline and then on weekly basis until wound healing or at 12 weeks, whichever came first. The baseline was defined the first visit when patient visited the wound clinic for the purpose of wound care. Wound assessment included measurement of length, width, and depth of the ulcer before and after debridement. If there was more than 1 ulcer, the largest ulcer meeting all the inclusion and exclusion criteria was enrolled. Other ulcers were treated in the same manner as the study ulcer. We evaluated wounds at each clinical visit to ensure the absence of infection. At each study visit the study coordinator took photographs of the wound, which were planimetrically measured using a 3-D imaging system (Silhouette, ARANZ Systems, Christchurch, New Zealand) and assessed by a clinician unaware of specific study allocation. This provides measures of wound area, length and width. Pre and post treatment photos were taken. Areas of new epithelium or partial thickness ulceration were not included. We estimated changes in wound area compared to previous visit wound size to estimate rate of weekly wound healing. An ulcer was considered “healed” when it is fully epithelialized with no drainage. Spontaneous daily physical activity was monitored using a validated and an unobtrusive wearable sensor (PAMSys™, BioSensics LLC, MA, USA; Figure 2)32 incorporated in a comfortable shirt (PAMShirt™) worn by participants for 48 hours at baseline and once every week for 48 hours until 12 weeks. Patient adherence in wearing the PAMShirt™ was assessed based on measuring acceleration fluctuation indicator of respiration as described in earlier publication.23 Activity was quantified by percentage of each main posture (i.e., sitting, standing, lying, and walking), total number of steps, number of unbroken walking episode, gait speed, longest unbroken episode of walking, number and duration of postural transition (i.e., sit-to-stand and stand-to-sit) per day.32-34 To examine whether the presence of DFU may limit spontaneous daily physical activities in DPN patients, the results of this study was retrospectively compared with our previous study23 in which similar activity monitoring protocol was used to monitor 48-hour spontaneous daily physical activities in 13 DPN patients without active ulcers (age: 59 ± ۸ years, BMI: 34.6 ± ۴٫۲ kg/m2 ). Results are expressed as mean ± standard deviation (SD). ANOVA and Fisher’s exact test (or chi-square, as appropriate) was used to examine between-group differences in descriptive data. Repeated measures ANOVA test was used to examine between-group differences in weekly wound healing outcomes. When a significant difference (defined as P < .050) was found the Student–Newman–Keuls correction was used as the post hoc test to assess pairwise comparisons. Spearman correlation coefficient was used to examine correlation between activity characteristics and wound outcomes. Logistic regression model (forward conditional) was used to identify significant activities predictors to successful wound healing. The person who analyzed the data was blind to the type of intervention. The collected physical activity data were also compared retrospectively with previously collected data7 from diabetic patients without foot ulcers (n = 13, age: 59 ± ۸, BMI: 34.6 ± ۴٫۲) to examine whether presence of foot ulcers may impact spontaneous daily physical activities. Statistical analyses were performed using SPSS® version 20 (IBM, Armonk, NY, USA).