Electrophysical therapy for managing diabetic foot ulcers: a systematic review

Abstract

To systematically assess published reports on the efficacy of electrophysical therapy in the treatment of diabetic foot ulcers, including electrical stimulation, low‐level laser therapy, therapeutic ultrasound and electromagnetic therapy. Databases searched included MEDLINE, CINAHL, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL) from 1966 to 2011. Studies reviewed included only randomised controlled trials (RCTs) on treatment with electrophysical modalities compared with sham, conventional treatment or other electrophysical modalities. Information extracted were objective measures of healing and data useful for the calculation of effect size. Eight RCTs were eventually included in the critical appraisal, with a combined total of 325 participants. Five studies were conducted on electrical stimulation, two on phototherapy and one on ultrasound. All studies reported that the experimental group was significantly more favourable than the control or sham group. The pooled estimate of the number of healed ulcers of the three studies on electrical stimulation compared to the control or sham electrical stimulation showed statistical significance [mean difference of 2·8 (95% CI = 1·5–5·5, P = 0·002] in favour of electrical stimulation. The results indicated potential benefit of using electrophysical therapy for managing diabetic foot ulcers. However, due to the small number of trials ever conducted, the possibility of any harmful effects cannot be ruled out, and high‐quality trials with larger sample sizes are warranted.

INTRODUCTION

More than 220 million people worldwide have diabetes; the World Health Organization (WHO) projected that deaths from diabetes will double between 2005 and 2030 (1). The lifetime risk for foot ulcers in people with diabetes could be as high as 25% (2). Diabetic ulcer may lead to persistent non healing ulcers, ending with amputation or even death (3). Over 70% of non traumatic lower limb amputations were performed in patients with diabetes that caused high morbidity and mortality (4). The financial burden is considerable; the implied cost of managing diabetic foot problems costs £252 million per year in the United Kingdom (2).

Peripheral neuropathy and ischaemia are the major causes of foot ulceration in people with diabetes. Neuropathy results in a loss of sensation and impaired microvascular circulation (5). Despite the application of various types of dressings, debridement, offloading or the performance of revascularisation surgery (6), a significant proportion of diabetic foot ulcers do not heal with these traditional treatment approaches. Physical modalities such as electrical stimulation, ultrasound and phototherapy offer an alternative approach to promoting the healing of chronic wounds to include diabetic foot ulcers; however, results of studies reported to date provide no conclusive remarks on its use, especially whether electrophysical therapy (EPT) is better used as an adjunct therapy or alone in the absence of other proven therapies in promoting the healing of diabetic foot ulcers.

EPT is one of the fundamental elements in the daily practice of physiotherapy, although the trend and usage of electrophysical modalities are not necessarily the same in countries such as USA, Canada and Australia (7). Commonly used EPT includes a variety of treatments ranging from electrical stimulation to the use of sound waves (ultrasound) and light (laser) to electromagnetic energy 8, 9. It has been used to promote tissue repair and has been found to enhance fibroblast activity (10) and angiogenesis (11). However, findings of studies conducted so far are still inconclusive and the clinical use for diabetic wound healing is still under investigation. Many of the conclusions from published works were in vitro 12, 13, from animal studies 14, 15 or on wounds caused by venous insufficiency and pressure ulcers 16, 17. Whether sufficient proof has been found in human diabetic foot ulcers is still unknown.

Thus far, there have been no published reviews or meta‐analyses evaluating the efficacy of electrophysical modalities in the treatment of diabetic foot ulcers. The aim of the current systematic review was to critically appraise published randomised trials designed to assess the efficacy of electrophysical modalities on the management of diabetic foot ulcers; and, if appropriate, to identify the most effective electrophysical modalities for managing these wounds.

METHODS

Data sources and searches

A search was conducted to identify relevant published studies. The databases searched included MEDLINE, CINAHL, EMBASE, PubMed and the Cochrane Central Register of Controlled Trials (CENTRAL) of the Cochrane Library. The databases were searched from their inception until November 2012. The search was restricted to articles published in English. Keywords and Medical Subject Headings (MeSH) used included ‘lower extremity’, ‘foot’, ‘foot ulcer’, ‘wound healing’, ‘diabetes mellitus', ‘diabetes complications', ‘diabetic foot', ‘physical therapy modalities', ‘electric stimulation therapy’, ‘electromagnetic(s) fields', ‘laser(s)’, ‘direct current', ‘phototherapy’ and ‘ultrasound’. (Appendix A) A manual search of bibliographic references of relevant articles and existing reviews was also conducted to identify studies not captured in the electronic database search.

Study selection

Published studies that reported the efficacy of electrophysical modalities in treating diabetic ulcers were eligible for inclusion. The inclusion criteria were as follows:

• 1The study design was a randomised controlled trial (RCT).
• 2The participants described as having diabetic ulcers, at any age, and in any care setting.
• 3Any electrophysical modalities were performed compared with sham treatment, conventional treatment or other electrophysical modalities.

The exclusion criteria were as follows:

• 1No inclusion criteria were described.
• 2Participants had a clinical diagnosis of wound other than diabetic origin.

Data extraction and quality assessment

Literature search was conducted by two reviewers (RK and SV) independently. Articles were screened according to the title, and then the abstract, followed by the full paper if necessary. Duplicates were checked and removed after excluding the publications that were clearly unrelated to the purpose of this study. The full text of publications satisfying the inclusion criteria was obtained for review. At all stages, whenever there is any disagreement between the two reviewers, they would resolve it by discussing between themselves, and sometimes with a senior and experienced reviewer (GC) and the corresponding author when necessary.

Each included paper was assessed for methodological quality by the same two reviewers, again independently, using a modified Jadad scale (18). Again, disagreements between them were resolved by consensus or through discussion with a senior researcher and the corresponding author. This scale includes 8 items designed to assess randomisation, blinding, withdrawals/dropouts, inclusion/exclusion criteria, adverse effects and statistical analyses. It has been widely used because it has the advantages of being simple, short, reliable and valid. The score for each article can range from 0 (lowest quality) to 8 (highest quality). Scores of 4 to 8 represent good to excellent (high quality). In addition to the items listed in the modified scale, the following data on aspects of quality were extracted:

• 1Evidence that a calculation of sample size was applied before the commencement of the trial
• 2Allocation concealment
• 3Use of intention to treat analysis

Details of the studies were extracted and summarised using a data extraction sheet. Attempts were made to obtain any missing data by contacting the authors of the studies. Data from studies published in duplicate were included only once. The data collection form consisted of items of demographic data (author, year published, country of study), data on the participants (sample size, age), electrophysical intervention, control intervention, duration of the intervention, follow‐up time, outcome measures, summary of the results and adverse effects.

Primary outcomes

Objective measures of healing were investigated, including the healing rate of diabetic foot ulcers; the time to complete healing; and the proportion of foot ulcers healed within the trial period.

Data synthesis and analysis

To assess the outcome of each study, the effect size was calculated. A meta‐analysis was only performed for the three studies on electrical stimulation 19, 20, 21 because of the heterogeneity of the treatment modalities and outcome measures used in the included trials. Effect size r was calculated using Review Manager (RevMan) (Version 5.0 Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2008) if means and standard deviations were available.

RESULTS

Search results

Using the pre‐defined keywords and MeSH, a total of 2832 publications pertaining to EPT for diabetic foot ulcers were found. Twenty‐two articles were excluded due to duplication. After reading the titles and abstracts, 2781 publications were considered irrelevant and excluded, leaving 30 for a full‐paper evaluation. Of these 30 articles, 22 were excluded because of the study design (non RCT; n = 11) and target population (non diabetic foot ulcers; n = 11). Finally, eight papers that specifically examined the effect of EPT on diabetic foot ulcer were critically appraised 19, 20, 21, 22, 23, 24, 25, 26. Figure 1 illustrates the trial selection process.

Figure 1.

Systematic reviews and meta‐analyses flow diagram of the literature search.

Characteristics of studies

Table 1 presents descriptive information on each of the studies reviewed. The trials were conducted between 1992 and 2011 in the U.S., Canada, Brazil and Iran. Six of the eight studies randomly assigned participants into two groups, with an intervention group receiving EPT and a control group receiving sham treatment 20, 21, 23, 24, 25, 26. Two studies assigned participants into three (22) and four groups (19) with different intervention approaches.

Table 1.

Outcomes of electrophysical modalities for treating diabetic ulcers

Overall, there were four trials on electrical stimulation 19, 21, 22, 23, one trial on ultrasound (24) and two trials on phototherapy 25, 26. The majority of them (6/8; 75%) were published after 2000. The mean age of the participants in the experimental groups was 59·8 years (range 30–82 years) and 60·3 years (range 30–87 years) in the control groups. Sample sizes in the experimental groups ranged from 7 to 32 (mean 23·9) and from 7 to 32 in the control groups (mean 17·2). The total sample size was 325 (n = 188 for the experimental groups, and n = 137 for the control groups) with 368 ulcers being treated.

The outcomes measured in the studies varied. The ‘percentage of wounds healed during the study period’ was measured by eight studies, ‘healing time’ by two studies; ‘blood flow’ by one study; ‘subject compliance’ by one study; ‘treatment time’ by one study; ‘ulcer granulation rate’ by one study; ‘number of patients with complete healing in each group’ by one study; and ‘difference between estimated and actual healing time’ by one study.

Methodological characteristics

Studies were graded into two categories of quality: (i) high‐quality studies with a modified Jadad scale score of 4 and above; and (ii) other studies with a modified Jadad scale score of 3 and below. After the review, there were five high‐quality trials, namely two on electrical stimulation, one on ultrasound and two on phototherapy 20, 21, 24, 25, 26. The summary of methodological quality is presented in Table 2.

Table 2.

Summary of methodological quality

Parameters	Baker et al.(19)	Ennis et al.(24)	Petrofsky et al.(23)	Lundeberg et al.(20)	Peters et al.(21)	Petrofsky et al.(22)	Minatel et al.(25)	Kaviani et al.(26)
Randomised	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes
Randomisation appropriate	Not described	Yes	Not described	Yes	Yes	Not described	Not described	Yes
Blinding	Yes	Yes	No	Yes	Yes	No	Yes	Yes
Blinding procedure	Not described	Double‐blinded	Not described	Double‐blinded	Double‐blinded	Not described	Double‐blinded	Double‐blinded
Withdrawals and dropouts	No	Yes	No	Yes	Yes	No	No	Yes
Inclusion or exclusion criteria	No	Yes	Yes	Yes	Yes	Yes	Yes	Yes
Adverse events reported	No	Yes	No	No	No	No	Yes	Yes
Method of statistical analysis	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes
Sample size calculation	No	No	No	No	No	No	No	No
Allocation concealment	No	No	No	No	No	No	No	No
Intention to treat analysis	No	Yes	No	Yes	No	No	No	No

Only four trials had a detailed explanation of how randomisation was carried out and provided an adequate report on the assignment of participants 20, 21, 24, 26. Five trials were double blinded to treatment allocation 20, 21, 24, 25, 26 and one trial did not report the subject blinding (23). Five studies clearly explained the reasons for withdrawals and drop‐outs, and reported drop‐out rates ranging from 10% to 59% 20, 21, 23, 24, 26. Moreover, only two studies indicated the number of withdrawals and the reasons for the withdrawals and drop‐outs, and followed the intention‐to‐treat principle 20, 24.

Efficacy of EPT

Electrical stimulation

The five electrical stimulation trials used different types of protocol. Two trials compared electrical stimulation with sham treatment 20, 21. Two trials by the same authors compared electrical stimulation with an infrared heat lamp or in a warm room 22, 23. The other trial compared two different protocols of electrical stimulation, with the control group receiving either very low levels of current or no electrical stimulation (19).

Lundeberg and co‐worker, Peters et al. and Petrofsky et al. investigated the treatment effect of electrical stimulation, but the authors did not provide information on calculations of sample size, or on allocation concealment 20, 21, 23.

The waveform used in the five trials included symmetrical biphasic, monophasic or square‐wave pulse. The healing rate was the main outcome for all of the five trials. Other outcomes included skin blood flow, compliance with the use of devices, proportion of wounds healed and time until the wounds healed. Four out of five trials found significant between‐group differences in healing rates, with the experimental groups in all these studies shown to be more favourable than the control groups 19, 20, 22, 23. The exception was the trial reported by Peters and collaborators, which showed no significant between‐group differences in healing rates (21).

Because of the heterogeneity of the outcome measures in two of the original articles 22, 23, the results in only three of the trials 19, 20, 21 was integrated by meta‐analysis by comparing the number of healed ulcers (Figure 2).

Figure 2.

The number of healed ulcer of the electrical stimulation versus sham electrical stimulation therapy or control group.

The mean differences of the number of healed ulcers in favour of electrical stimulation in these studies were 2·4 [95% confidence interval (CI) = 0·91–6·2), 3·2 (95% CI = 0·88–11·5) and 3·5 (95% CI = 0·94–12·7], respectively, between people receiving electrical stimulation and people receiving a sham or control treatment. The pooled estimate of the treatment effects of electrical stimulation compared to sham electrical stimulation or a control treatment was statistically significant with a mean difference of 2·8 (95% CI = 1·5–5·5, p = 0·002).

Ultrasound

The study on ultrasound was a high‐quality trial. The researchers compared the efficacy of a 40 kHz ultrasound device with a sham device that delivered a saline mist without producing ultrasound for managing diabetic foot ulcers (24).

Both the experimental and sham groups showed improvement from pre‐treatment to post‐treatment in the proportion of wounds healed, with the healing of the treatment group (40·7%) differing significantly from that of the control group (14·3%) (P = 0·0366). In addition, the experimental group healed significantly more quickly [mean time to heal 9·1 (SD = 0·58) weeks] than did the sham group [mean time to heal 11·7 (SD = 0·22) weeks] (log rank P < 0·0144).

Ennis et al. reported that ultrasound therapy produced a significant improvement in the proportion of wounds healed and time required to heal; however, they did not provide any details on the calculation of their sample size (24).

Phototherapy

Minatel et al. examined the efficacy of phototherapy, with a combination of 660 and 890 nm lights, whereas Kaviani et al. investigated the effect of low‐level laser therapy in promoting the healing of chronic diabetic ulcers as compared to a sham group 25, 26.

Minatel and colleagues reported a significant improvement in ulcer granulation and healing rates. The mean ulcer granulation and healing rates were significantly higher for the experimental group than the sham group throughout the course of the treatment (P < 0·02). After the whole course of treatment, 58·3% of the experimental group with ulcers was completely healed and three‐quarters achieved 90–100% healing. By contrast, in the sham group with ulcers, none of them attained more than 90% healing. The author concluded that the combination of 660 and 890 nm lights promoted tissue granulation and the rapid healing of diabetic ulcers. However, their study did not provide details on the randomisation method, calculation of sample size, allocation concealment, intention to treat analysis or the number of participants who commenced and completed the study (25).

The study by Kaviani and colleagues also reported a significant improvement in terms of the number of patients whose ulcer completely healed and the mean reduction in ulcer size. By week 4, the reduction in ulcer size in the treatment group was significantly greater than the control group (P = 0·046). By week 20, all patients in the treatment group had complete ulcer healing while three patients in the control group experienced complete healing. The author concluded that laser could be a safe adjunct therapy to patients with diabetic foot ulcers (26).

Adverse effects

None of the trials conducted on electrical stimulation reported any adverse events. For the ultrasound study conducted by Ennis et al., a total of 193 adverse events were reported in all study groups, including the development of cellulitis, the development of additional wounds on the index foot, wound drainage and erythema (24). With 83% of the events not related to the device, the remaining possibly device‐related events included pain, erythema, enlargement of ulcers, wound infection and the development of additional blisters and oedema. The therapeutic outcomes and adverse events associated with these trials are presented in Table 2. No adverse event was found in the two studies undertaken with phototherapy 25, 26.

DISCUSSION

The use of EPT, including electrical stimulation, ultrasound, laser and electromagnetic energy for healing wounds has drawn attention from physical therapists. This systematic review is the first to investigate the efficacy of electrophysical modalities in treating diabetic foot ulcers.

Electrical stimulation has been used to manage diabetic foot ulcers that do not respond to standard wound treatments 19, 20, 21, 22, 23. Using modified Jadad scale, the trial of Lundeberg et al.(20) and Peter et al.(21) were assessed as of high quality. However, in the study conducted by Baker et al. the initial analysis revealed no difference between groups. The authors then modified the analysis by restricted to wounds with healing rates <90% per week and eliminated the subjects that did not receive at least 30 minutes treatment per day (one‐third of the original protocol); however, there were still no significant difference between groups. Until the authors combined the control group received either no stimulation or low‐level stimulation, a significant difference between groups was detected. They did not include a group that received no stimulation, thus we cannot rule out the effect of low‐level stimulation (19).

The study by Petrofsky et al. included heat therapy as part of the standard care program; yet the individual roles of heat and electrical stimulation in the wound could not be identified. Another study done by the same author later in 2010 showed that the application of local heat alone could increase the rate of diabetic foot ulcer healing, as in the group of electrical stimulation with heat therapy (23); thus, the effect of electrical stimulation on diabetic foot ulcers might have been confounded in the previous study.

One major limitation that exhibited in all the eight studies reviewed was that none of the studies provided any information on the calculation of sample size or allocation concealment. Similarly, the studies performed by Baker et al. and Petrofsky et al. did not report details on how randomisation and blinding was performed. Furthermore, there was a lack of information on withdrawals and adverse effects, calculation of sample size, allocation concealment and the use of intention to treat analysis 19, 22, 23. Note that in the high‐quality study by Peters et al.(21), the between group difference in terms of percent of patients healed was marginally non significant (P = 0·058) but difference was found when treatment compliance was considered (P = 0·037); thus, we could not eliminate the possibility of beneficial effect demonstrated by the electrical stimulation (21). The results of our meta‐analysis support the efficacy of electrical stimulation on the healing of diabetic ulcers in human subjects 19, 20, 21.

Minatel and colleagues examined the effect of lasers and reported a significant improvement in ulcer granulation and healing rates, but they did not provide details on the randomisation method, calculation of sample size, allocation concealment, the intention to treat analysis or the number of participants who started and finished the study (25). Kaviani et al. also reported the significant effect of lasers in mean ulcer size reduction; however, whilst they reported the withdrawal and dropout rate no intention to treat analysis was reported (26). It has been considered a non invasive treatment with no reported side effects. However, there is still little agreement on a protocol for wound healing.

Therapeutic ultrasound has been widely used to manage many musculoskeletal conditions in clinical settings, but with conflicting results. The clinical use of ultrasound to promote wound healing is still under investigation. The possible mechanism of ultrasound in promoting tissue repair is likely to be due to its mechanical effect, with micromassage changing the permeability of membranes and stimulating the proliferation of fibroblasts (13). Ennis et al. reported significant improvements in the proportion of wounds healed and the time required to heal with ultrasound treatment, and the effects were also considered convincing by a modified Jadad scale; however, no details were provided on the calculation of sample size (24). The equipment used in this study was a unique non contact non‐thermal acoustic therapy (24), which is different from the type of ultrasound commonly used (27). Also, 50% of the originally recruited patients were excluded during the audit process due to protocol error. These subjects were not included in the final analysis. Interpretation of the results should, therefore, be careful because this is an essential element directly related to the reduction of bias.

No RCTs were found in using electromagnetic therapy for treating diabetic foot ulcers. Only a single RCT published investigating the efficacy of electromagnetic therapy for treating diabetic stump wound and no significant benefit was reported (28). The pathology and prognosis of the diabetic stump wound may be different from that of chronic foot ulceration. Also, the use of electromagnetic therapy does not elicit any complications from direct contact with the electrodes that are adopted by other electrophysical modalities. Indeed, electromagnetic therapy can be applied in the presence of casts or wound dressings, with a low risk of infection (27), further research is warranted before dismissing any beneficial effects from this therapy.

A number of animal studies have reported that electrical stimulation (29), lasers (30) ultrasound (31) and electromagnetic therapy (32) enhance tissue repair in diabetic ulcers. Conversely, other animal studies have shown no significant differences in healing between treated diabetic ulcers and control wounds (33). Research on EPT has mostly been done on animal wounds consisting of surgically excised skin. These experimental wounds excluded common problems associated with delays in healing such as ischaemia, infection, necrotic debris or sinus formation. Therefore, these animal wound models may not be ideal for studying the effect of EPT on human diabetic ulcer healing (34).

Diabetic foot ulceration was associated with multiple causes included neuropathy, peripheral vascular disease or a combination of both (35). The difference in aetiology might affect the management and treatment effect of different electrical modalities. Subjects with neuropathic or mixed (venous and arterial) ulcers were included in two high‐quality studies 22, 25. Another high‐quality study on ultrasound included chronic diabetic ulcer by screening the subjects with ankle brachial index for excluding the ischaemic component to the wound aetiology (24). In the study by Lundeberg and colleagues, the subjects included suffered from ‘diabetic leg ulcers due to venous stasis' and ‘patients were excluded when there was venous ulcer due to trauma, osteomyelitis, abscess or gangrene or ankle pressure below 75 mm Hg’(20). Petrofsky et al. excluded patients with peripheral vascular disease (23). Whereas the other three studies reviewed did not provide any detailed information on the aetiology of the ulcers 19, 21, 26. Owing to the different aetiology of diabetic foot ulcers in the studies, interpretation of the results and the generalisability to patients with diabetes should be made cautiously.

Classification of diabetic foot ulcers is important in describing the lesions that we treat, in order to monitor the progress of the treatment and the prognosis, as well as to ensure that the study population is homogeneous (36). In the most widely accepted and universally used grading systems specified on diabetic foot ulcers, [Wagner–Meggitt system (37) and the University of Texas Diabetic Wound Classification System (38)], the stages are separately identified and classified according to the presence of ischaemia, infection or both. Among the reviewed studies, only Ennis et al. and Kaviani et al. indicated that subjects with Wagner grade 1 or 2 wounds were recruited, while Peters et al. recruited subjects with grade 1A–2A wounds under the University of Texas Diabetic Wound Classification System 21, 24, 26. None of the studies evaluated the stage of the wounds by the end of the treatment, although this might be an important outcome measure in monitoring the progress of diabetic ulcers. The high‐quality study by Minatel et al. included diabetic ulcers also from the lower leg. Hence, the sample might not be homogenous enough to compare and draw conclusions that phototherapy is beneficial to patients with diabetic foot ulcers.

The choice of treatment parameters and the dosage of various electrophysical therapies for managing various human wounds are still uncertain. Many existing studies did not provide complete details on the characteristics of the treatment, including the staging of diabetic foot ulcers, how diabetic foot ulcers are diagnosed or the condition of wounds with different dressings. Different uses of wound dressing, for example hydrogels might influence the rate of healing by providing the warm moist environment 39, 40. Using saline‐moistened gauze dressing in the ultrasound therapy is not a standard care in clinical practice (24) and none of the studies reviewed had matched the dressing to the moisture of the wound during the study period. The International Working Group of the Diabetic Foot also stated that medical management such as hyperbaric oxygen therapy, negative pressure wound therapy 41, 42 and offloading that could relieve the plantar pressure (42) may be beneficial to wound healing. However, none of the eight studies included considerd the principles of ulcer treatment in addition to the EPT utilised. This leads to uncertainty concerning the effectiveness of the electrical modalities when different medical management was used in combination.

The present review demonstrates methodological shortcomings in RCTs on the efficacy of EPT included those by electrical stimulation, phototherapy and ultrasound in healing diabetic foot ulcers. It is remarkable that none of the studies provided information about calculations of sample size and allocation concealment. Furthermore, small sample sizes could lead to low statistical power and allocation concealment has been shown to be associated with exaggerated treatment effects 43, 44. As withdrawals and dropouts are essential elements directly related to the reduction of bias, the characteristics of the participants leaving the study should be examined in detail in future RCTs.

Interpretations of studies with poor methodological quality must be regarded with caution when applied clinically. While the studies eventually included in the present systematic review were evaluated by a modified Jadad scale, we also applied the PEDRO scale to the studies (detailed results not shown) for double checking purposes. Both scales showed very similar results in terms of the methodological quality of the studies. There is a clear need for well‐designed RCTs examining EPT for diabetic ulcers. Trials should be clinically meaningful and adequately powered. Furthermore, because of the heterogeneity of the aeitology of diabetic foot ulcers in the studies reviewed, the results found probably cannot be generalised to all patients with diabetes; readers would need to be cautious when considering how these results can be applied in their own clinical setting. Investigators should consider the findings of this systematic review when designing future studies and attempt to overcome the limitations of the studies presented, by using true randomisation, blinded assessment, allocation concealment, intention to treat analysis and by paying attention to withdrawals and dropouts. In addition, the procedures for diagnosing diabetic foot ulcers, and the stage of the foot ulcers, and the details in standard care should be described. On the basis of the positive effects of electrical stimulation, lasers and ultrasound treatment, high‐quality trials with larger sample sizes are warranted in these areas.

LIMITATIONS

In this review, the search was restricted to English publications, which may have resulted in a language bias (45). The heterogeneity in sampling and treatments among studies, as well as the limited number of studies, small sample sizes and poor methodological quality of some of the studies, limit the overall conclusion made on the efficacy of EPT on managing diabetic foot ulcers. This highlights the importance of further research.

CONCLUSION

There is inadequate evidence to support the use of EPT for promoting the healing of diabetic foot ulcers. Very few studies have been conducted for each modality and they have small sample sizes. The three studies on electrical stimulation included in the meta‐analysis are either underpowered or methodologically weak, and only a few studies were conducted on other electrophysical modalities such as ultrasound and lasers. However, the positive findings reported by these studies using electrical stimulation, phototherapy and ultrasound interventions are sufficient to encourage high‐quality RCTs with larger sample sizes in these areas.

ACKNOWLEDGMENTS

This project was supported by the General Research Fund provided by Research Grants Council of the Hong Kong SAR Government (PolyU 512607, PolyU 560011).

APPENDIX A: DETAILED SEARCH STRINGS

Basic search was combined with searches for specific interventions by adding the search term AND

Basic search

((Diabetes Mellitus [MeSH]) OR (Diabetes Mellitus) OR (Diabetes) OR (Diabetic) OR (Diabetes Mellitus, Type 2)) OR (Diabetes Complications [MeSH]) AND (lower extremity [MeSH]) OR (Foot [MeSH]) AND (ulcer [MeSH]) OR ((Foot ulcer) OR (diabetic foot) OR (wound healing [MeSH]) OR (wounds and injuries [MeSH])) AND (randomised controlled trial [MeSH]) OR (controlled clinical trial) OR (random allocation) OR (clinical trial) OR (comparative study)

Electrical stimulation

(Physical therapy modalities [MeSH]) OR (Electric stimulation therapy [MeSH]) OR (Electric* therapy) OR (Microamperage stimulation) OR (Low intensity direct current) OR (High voltage) OR (electrotherapy) OR (direct current).

Electromagnetics

(Electromagnetics [MeSH]) OR (Electromagnetic*) OR (Electromagnetic Fields) [MeSH] OR (Magnetic Field Therapy) OR (Pulsed electromagnetic therapy).

Phototherapy

(Ultraviolet rays [MeSH]) OR (Lasers [MeSH]) OR (Laser Therpy [MeSH]) OR (Laser Therapy, Low‐Level [MeSH]) OR (MIRE) OR (monochromatic infrared energy) OR (Phototherapy [MeSH]) OR (Infrared Rays [MeSH]) OR (Anodyne).

Ultrasound

[Ultrasound (MeSH)] OR [Ultrasonic Therapy (MeSH)] OR (Ultrasonic Therap*) OR (ultrasonic).