DOI: 10.1111/eci.12685
ORIGINAL ARTICLE
The wound healing trajectory and predictors with
combined electric stimulation and conventional care:
one outpatient wound care clinic’s experience
Kehua Zhou*,†, Ronald Schenk‡ and Michael S. Brogan‡
*
Physical Therapy Wound Care Clinic, †Department of Health Promotion, ‡Department of Physical Therapy, Daemen College,
Amherst, NY, USA
ABSTRACT
Background Electric stimulation (E-stim) has been found to be an effective treatment in improving wound
healing rates. However, the wound healing trajectory and its related predictors for complete wound closure
(CWC) have not been reported with E-stim treatment.
Materials and methods This was a retrospective study. Data on 159 patients treated at an outpatient
wound clinic utilizing combined intervention of E-stim and conventional care were included. The Kaplan–
Meier healing curve together with linear regression models depicted the percentage of patients with CWC
against time.
Results With 100, 112 and 140 days of treatment, the percentages of patients with CWC were 5912%,
6101% and 6541%, respectively. Linear regression models predicted that all patients would achieve CWC by
2155, 2226 and 2480 weeks, respectively. The speed for the increase in the number and percentage of
patients with CWC peaked between 50–75 days of treatment. To optimize timely healing, referral to other
treatment facilities or change of treatment protocol is warranted around the peak time. With the combined
intervention of E-stim and conventional care, positive predictors for CWC included a shorter wound duration at
initial evaluation (P = 0005, OR = 310), better compliance with appointments (P = 0007, OR = 338) and the
diagnosis of venous leg ulcer (P = 0001, OR = 388).
Conclusions This study provided preliminary data on wound healing trajectory and predictors with combined
E-stim and conventional care. E-stim seemed to expedite wound healing; however, further research studies are
needed.
Keywords Complete wound closure, electric stimulation, predictors, trajectory, wound healing.
Eur J Clin Invest 2016; 46 (12): 1017–1023
Introduction
Wounds are skin injuries caused by trauma, surgery and other
pathological factors [1]. Based on wound duration, wounds
may be classified as acute wounds, chronic wounds and nonhealing wounds. Acute wounds usually heal in a sequential
and timely manner, whereas the healing of chronic wounds is
usually disrupted at various phases of the wound healing
process [1]. Although specific definitions differ in research
reports, chronic wounds generally refer to wounds that fail to
close in 3 months and hard-to-heal wounds refer to wounds
with a duration of 6 months and beyond [2,3].
Methods presently being used to treat chronic wounds
include negative pressure wound therapy, debridement, local
antibiotic therapy and moist dressing application [3–6]. Other
widely used advanced therapies include bioengineered skin
substitutes and materials, electrical stimulation (E-stim), and
advanced drug delivery systems [3–6] Although new and more
effective treatments are available for wounds, the conflict
between cost and efficiency continues as does the need for
high-quality research to prove the efficacy of various wound
treatments [3–7].
As a result, delayed healing of wounds continues to
impairlives and, in some cases, causes death [7]. Based on
previous research studies, E-stim appears to be an effective
treatment in improving wound healing rates [8]. However,
large and high-quality randomized controlled trials are still
needed to prove the efficacy and efficiency of E-stim in
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K. ZHOU ET AL.
wound care [8]. Wound care studies utilizing E-stim have
focused on various outcome measures including absolute
and percentage of wound area remaining; however, complete
or 100% wound closure (CWC), which is recognized as the
most stringent criterion to determine the efficacy for a
wound healing agent or treatment, is typically not
reported [9].
With CWC as the outcome measure, Robson et al. [9]
suggested that researchers could predict the effectiveness of
treatments. Based on results of previous studies for the efficacy of pharmaceutical or surgical interventions, percentages
of all patients achieved CWC against time have been
reported as the following: 52% by 32 weeks in diabetic foot
ulcers (DFU) [9], 42% and 75% at 6 and 12 months in surgical wounds for arterial insufficiency [10], 17% by 112 days
in pressure ulcers [11] and 60% by 20 weeks in venous leg
ulcers (VLU) [12]. Correspondingly, researchers predicted
CWC in all patients by 37 weeks in DFU [9], 110 weeks in
pressure ulcers [11] and 31 weeks in VLU [12]. However,
the wound healing trajectory and its related predictors
for CWC have not been reported in patients treated with
E-stim.
Wound healing trajectories depict probabilities for patients
reaching CWC at a specific time point during treatment and
thus provide patients and clinicians with a better outlook of
the wound healing process. Nonetheless, probabilities for
patients reaching CWC are influenced by patient demographics and wound history. Based on mathematical models
and clinical data on conventional care, researchers proposed
that wound size, age, elapsed time from wound appearance to
the beginning of the treatment, initial healing rate during the
first 2–4 weeks of treatment, skin perfusion pressure, body
mass index (BMI), type of treatments and others may be
related to and are important prognostic factors in wound
healing [13–22]. Nonetheless, specific predictors differ in the
literature [13–22], and understandings of factors affecting
wound healing using E-stim are limited. To our best knowledge, only one study reported prognostic factors in wound
healing with E-stim, which included wound size, patient’s
age, elapsed time from wound appearance to the beginning of
the treatment, width-to-length ratio, location and type of
treatment [23].
This study summarizes data from patients treated at a
physical therapy outpatient wound care clinic where combined
E-stim and conventional care were utilized. The purposes of the
present study were to (i) provide the wound healing trajectory
using plot of percentage of patients with CWC against treatment duration, (ii) establish linear regression models for the
prediction of treatment duration needed for all patients reaching CWC, (iii) identify possible predictors for wound healing
with the combined intervention.
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Subjects and methods
The study was part of a large project exploring cost efficacy of
wound care at the Daemen College Physical Therapy Wound
Care Clinic. The study protocol was approved by the Daemen
College Institutional Review Board prior to data extraction.
Patient data from 10 September 2012 to 23 January 2015 were
extracted and analysed. The actual cost and CWC rate of
wound care at the present clinic were presented in a different
study [24]. This study presented the results of analyses related
to the wound healing trajectory and its predictors.
Previous studies depicting wound healing trajectories were
part of large clinical trials exploring the effectiveness of specific
interventions [9,11,12]. These clinical trials had strict inclusion
and exclusion criteria. Patients with unstable vital signs were
likely to be excluded prior to study participation [9,11,12].
Similarly, this study excluded patients with unstable vital signs
which warranted hospitalization and advanced care and
thereby were unable to continue outpatient care at the present
clinic. Additionally, patients with the following conditions
were also excluded: (i) patients being treated at the present
clinic at the time of data extraction, (ii) patients lost to followup and had no more than six documented visits. In addition to
the conciliation measure between efficacy assessment and bias,
the main reason for these exclusions relates to the difficulties in
establishing a direct link between the status of these wounds
and intervention at the clinic. In this study, wound healing
status was marked as CWC or remaining open upon discharge;
patients with more than two unjustifiable cancellations (no
shows) were considered as noncompliant. For patients with
more than one wound, only the wound with the longest
duration was used for analyses.
Statistical methods
Patients’ demographics and wound treatment history were
summarized and described. Quantitative data were expressed
with mean SD and were compared using t-tests between
groups. Categorical data were summarized and compared with
Fisher’s exact test. Odds ratios (OR) with 95% confidence interval (CI) were presented as measures of effect size. The Kaplan–
Meier healing curve was utilized to depict the percentage of
patients achieving CWC against days of treatment. In previous
studies, researchers utilized both 112 and 140 days as cut-points
for the creation of linear regression models to test treatment
efficacy [11,12]. With reference to these studies, the percentages
of patients with CWC were computed for time points of 100, 112
and 140 days of treatment and three different linear regression
models were employed to assess the treatment duration needed
for all patients reaching CWC. A two-tailed P < 005 was considered statistically significant. All data were analysed with
SPSS 17.0 software (SPSS Inc., Chicago, IL, USA) for Windows.
ª 2016 Stichting European Society for Clinical Investigation Journal Foundation
THE TRAJECTORY AND PREDICTORS IN WOUND HEALING USING ELECTRIC STIMULATION
closure date prior to discharge was considered as the date for
CWC.
Results
From 1 September 2012 to 23 January 2014, 261 patients were
evaluated and treated at the present clinic. Among these
patients, 102 patients were excluded from the present study
due to the following reasons: transfer to advanced care due to
unstable vital signs and inability to continue outpatient care at
the present clinic (n = 55), being treated at the time of data
extraction (n = 25), no show after one to six visits (n = 17), no
wound (n = 2), treatment duration of significantly long period
beyond others thus being considered as outliers (n = 3). Consequently, 159 patients (77 males and 85 females) with an age of
6378 1735 years were included.
High-voltage pulsed-current electric therapy (RichMar
Winner EVO ST4, Chattanooga, TN, USA), 120 pps, 100 mA,
continuous wave for 45 min and conventional wound care
were used in almost all patients two to three times a week.
Cathode was placed on top of the wound with a wet
(saline) gauze interface; anode was usually placed over the
nearby skin. The intensity of E-stim was adjusted based on
patients’ tolerance. Whirlpool therapy, ultrasound and
ultraviolet therapy were occasionally used based on the
clinician’s evaluation of wound conditions. Collagen and silver-based dressings were commonly applied. Additional
four-layer compression dressings together with Unna boot
were used in VLU if compressible. As a clinical routine, all
patients were treated at the clinic for one or more visits
after CWC to prevent relapses and the most recent wound
Patient demographics
Patient demographics were provided in Table 1. Regarding the
wound type in these patients, 72 (4528%) patients had VLU; 48
(3019%) patients had wounds of traumatic or surgical aetiology;
11 (692%) patients had pressure ulcers; 16 (1006%) patients had
DFU; and 12 (755%) had other wounds including one patient
with second-degree burn, five patients with pilonidal cyst
wounds and six patients with arterial wounds (Fig. 1).
The wound healing trajectory and linear
equation models
The histogram (Fig. 2) and the Kaplan–Meier healing curve
(Fig. 3) depict the actual number and percentage of patients
with CWC against days of treatment; the increases in the
number and percentage of patients with CWC do not follow a
linear pattern. The associated curve of the histogram peaks
between 50 and 75 days of treatment. The inclination ratio of
the Kaplan–Meier healing curve decreases after 100 days of
treatment as demonstrated via the inclination ratios of the linear regression models using the three cut-points at treatment
day 100, 112 and 140 (Table 2).
At the cut-point of 100 days of treatment, 94 of 159 (5912%)
patients reached CWC. Based on the corresponding linear
regression equation for percentage of patients with CWC
[Y1 = 0141 + 0662 (Day)], all patients were expected to
Table 1 Patient demographics and comparison between CWC and non-CWC
Characteristics
CWC
(n = 119)
N
Gender (female/male)
Non-CWC
(n = 40)
P value (OR, 95% CI)
74/85
66/53
18/22
0.276 (1.52, 0.74–3.13)
Wound duration (days) (< 180/≥ 180)
110/49
90/29
20/20
0.005 (3.10, 1.47–6.56)
Marital status (currently married Y/N)
67/92
48/71
19/21
0.463 (0.75, 0.36–1.54)
Living status (alone/others)
44/115
37/82
7/33
0.107 (2.13, 0.86–5.25)
76/43
28/12
0.566 (0.76, 0.35–1.64)
Education level (< 4year/≥ 4year college)
104/55
BMI (< 25/≥ 25)
31/128
20/99
11/29
0.167 (0.53, 0.23–1.24)
# of concomitant disease (≤ 2/> 2)
60/99
48/71
12/28
0.264 (1.58, 0.73–3.40)
131/28
104/15
27/13
0.007 (3.38, 1.42–7.85)
Pain at evaluation (yes/no)
72/87
57/62
15/25
0.276 (1.53, 0.74–3.19)
Number of wounds (1/≥ 2)
88/71
61/58
27/13
0.10 (0.51, 0.24–1.08)
Venous leg ulcers (yes/no)
72/87
63/56
9/31
0.001 (3.88, 1.70–8.84)
63.78 17.35
64.09 16.92
62.85 18.74
Patients’ compliance (yes/no)
Age (years)
0.315
#, number; OR, odds ratio; CWC, complete wound closure.
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Figure 1 The pie chart depicts the breakdown of wound
diagnoses in patients.
Figure 3 The Kaplan–Meier healing curve depicts the
cumulative percentages of patients of the sample reaching
complete wound closure against days of treatment. The
inclination ratio appears decreasing after 100 days of
treatment.
140 days, 104 patients (6541%) achieved CWC and the linear
regression equation model for percentages of patients with
CWC Y3 = 4332 + 0551 (Day) predicts all patients reaching
CWC projected at 17362 days (2480 weeks) after treatments.
Comparisons between patients with and without
CWC upon discharge
Figure 2 The histogram depicts the number of patients with
complete wound closure during each time period. The
associated curve of the histogram peaks between 50 and
75 days of treatment.
achieve CWC by 15084 days (2155 weeks) of treatments. At
the cut-point of 112 days of treatment, 97 of 159 (6101%)
patients reached CWC, and using the corresponding linear
regression equation Y2 = 1074 + 0635 (Day), we could predict
that all patients will achieve 100% wound closure by
15579 days (2226 weeks) of treatment. At the cut-point of
1020
Upon patient discharge, 119 (7484%) patients healed with
CWC and 40 (2516%) patients did not (Table 1). Time for CWC
in these 119 patients was 7245 6422 days. Compared to the
patients without CWC upon discharge, patients with CWC
presented with a shorter wound duration at initial evaluation
(≥ 180 days, OR = 310, P = 0005) and a higher proportion
with VLU (OR = 388, P = 0001), and better compliance with
appointments (OR = 338, P = 0007). No significant differences
were found between the two groups in other variables (P > 005
for all, Table 1).
Discussion
The Kaplan–Meier healing curve was used to depict the healing
trajectory for CWC in patients receiving combined E-stim and
conventional care for the first time in the literature. The
ª 2016 Stichting European Society for Clinical Investigation Journal Foundation
THE TRAJECTORY AND PREDICTORS IN WOUND HEALING USING ELECTRIC STIMULATION
Table 2 Linear regression models with different cut-points of treatment
Cut-points (Days)
Patients with
CWC
100% patients with
CWC
N
%
Days
Weeks
Linear regression equation for %
patients with CWC
R2 value
100
94
5912
15084
2155
Y1 = 0141 + 0662 (Day)
0965
112
97
6101
15579
2226
Y2 = 1074 + 0635 (Day)
0960
140
104
6541
17362
2480
Y3 = 4332 + 0551 (Day)
0927
CWC, complete wound closure.
inclination ratios of the established linear regression models
decreased in order: 0662 at 100 days, 0635 at 112 days and
0551 at 140 days. Together with the information from the histogram and the Kaplan–Meier healing curve, the healing speed
for the increase in the percentage of patients with CWC slowed
after 50–75 days of treatment. These results are consistent with
wound measurement reductions in the first 2–4 weeks of
treatment being a predictor for wound healing in previous
studies [15–17].
With 100, 112 and 140 days of treatment, the percentages of
patients with CWC were 5912%, 6101% and 6541%, respectively. The linear regression models correspondingly predicted
all patients would achieve CWC by 2155, 2226 and
2480 weeks. The predicted results using linear regression
models differed from the actual clinic data as many patients
reached CWC and were discharged after 2480 weeks, and
some were discharged without CWC even after 40 weeks of
treatment (Fig. 3). Thus, these results indicate that to optimize
timely healing, patients should be referred to other settings or
treated with different interventions which may include surgery,
hyperbaric oxygen therapy, advanced wound care dressing and
others, after around 50–75 days of treatment using this combined intervention. Nonetheless, the definitive time for patient
referral or change in treatment plan deserves further
investigation.
Using wound healing trajectories, Robson et al. [9] reported
that 52% of patients with DFU achieved CWC by 32 weeks and
all patients were predicted to achieve CWC by 37 weeks. In a
study about pressure ulcer, Payne et al. [11] found that 81% of
all patients reached 90% wound surface reduction at 112 days
(percentage of patients with CWC not reported) and predicted
that all patients would achieve CWC by 110 weeks. In regards
of venous ulcers, researchers found that 60% patients achieved
CWC by 20 weeks (140 days) and 31 weeks were expected for
all patients to reach CWC [12]. After infrainguinal bypass with
reversed saphenous vein for critical limb ischaemia, Chung
et al. [10] reported that the percentages of patients achieving
CWC were 42% and 75% at 6 and 12 months, respectively, for
surgical wounds. Interestingly, compared with these previous
studies [9–12], the percentages of all patients with CWC were
higher and the predicated treatment durations for all patients
with CWC using the regression models were shorter at 100, 112
and 140 days of treatment in present study. Although comparisons with these previous studies may not be appropriate
[9–12], the present study provided preliminary data regarding
the speed and effectiveness of this combined intervention
which appears to be a reasonable and promising treatment
protocol for wounds. The results of the present study may thus
provide additional support to the previous finding that E-stim
facilitates wound healing [8].
In the present study, wound duration at initial evaluation
(≥ 180 days, OR = 310, P = 0005), the diagnosis of VLU
(OR = 388, P = 0001) and patient compliance (OR = 338,
P = 0007) are three significant predictors for CWC with the
combined intervention. Our results add further information
for the prediction of wound healing using patient demographics and wound history. These findings are consistent
with previous literature regarding elapsed wound duration
from wound appearance to the beginning of treatments
[13,21,23]. Although compliance is generally recognized as an
important factor for patient care, patient compliance as an
important predictor for wound healing is not reported in
previous studies. In the present study, compliance is defined
as compliance to patients’ appointments; the present study
provides the first research-based evidence that patients with
good compliance are 338 times more likely to have their
wounds closed than patients without. The result that VLU are
more likely to reach CWC as compared to other types of
wounds indirectly supports the available research regarding
the relatively rapid wound healing in VLU [12]. These similar
findings with previous studies of conventional wound care
indicate that the addition of E-stim does not alter the influences of wound duration, the diagnosis of VLU, and patient
compliance on wound healing.
Additional factors affecting wound healing using E-stim may
include variations in type, parameter and location of electric
stimulation which were not investigated in the present study.
Further analyses of data acquired at the present clinic revealed
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K. ZHOU ET AL.
that patients with predominant inflammation of the wound(s)
lacked optimal response to E-stim treatment [25]. Nonetheless,
optimal parameters and type of E-stim together with its specific
indications for wound healing deserve further investigation.
Limitations
The exclusion criteria may alter the results of the present study
and may be unjustifiable, but they could be considered as a
conciliation between efficacy assessment and statistical bias.
The present study was based on data captured at one outpatient clinic. Due to sample size, no subgroup analyses were
performed based on wound types. Nonetheless, results of the
present study may be of value in our clinical decision-making.
As E-stim is getting popular in wound management [8], results
of the present study may also provide valuable information for
clinical wound management using combined intervention with
both E-stim and conventional care.
Conclusion
The present study provided preliminary data on wound healing trajectory and predictors with combined E-stim and conventional care. E-stim seems to expedite wound healing;
however, further research studies are needed.
Acknowledgements
The authors would like to thank the John R. Oishei Foundation
and the James H. Cummings Foundation for funding the Daemen College Physical Therapy Wound Care Clinic, Dr. Corstiaan Brass for his generous donation to the clinic and guidance
in patient management and various suppliers for wound
dressings. The clinic which is located in Cheektowaga, NY,
provided free care to patients with chronic wounds for two
years.
Disclosure
No competing financial interests exist.
Address
Physical Therapy Wound Care Clinic, Daemen College,
Amherst, NY 14226 (K. Zhou); Department of Health Care
Studies, Daemen College, Amherst, NY 14226, USA (K. Zhou);
Department of Physical Therapy, Daemen College, Amherst,
NY 14226, USA (R. Schenk, M. S. Brogan).
Correspondence to: Kehua Zhou, Physical Therapy Wound
Care Clinic, Daemen College, 4380 Main Street, Amherst, NY
14226, USA. Tel.: 716-671-8073; fax: 716-671-8074; e-mail:
kzhou@daemen.edu
Received 29 September 2015; accepted 2 October 2016
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