|
Background
Chronic wounds (e.g., diabetic ulcers, pressure ulcers, and venous ulcers) are common in both acute as well as community healthcare settings. The management of these chronic wounds entail many approaches. Cushions, mattresses, and pressure-relieving supporting surfaces/beds are often used as measures for the prevention and treatment of pressure sores; compression therapy in a variety of forms is frequently employed for venous leg ulcer prevention and treatment; and a wide range of therapies including ultrasound is also used in managing chronic wounds. In August 2004, the MIST Therapy System 5.0 (Celleration, Inc., Eden Prairie, MN), a low-frequency, non-contact ultrasound device, was cleared for marketing by the United States Food and Drug Administration. It is indicated for wound cleaning and maintenance debridement of wounds containing yellow slough, fibrin, tissue exudate, or bacteria.
Although therapeutic ultrasound has been used clinically to enhance healing of chronic wounds, no consensus exists regarding its effectiveness.
In a placebo-controlled, single-blinded, clinical study, Peschen and associates (1997) examined the effect of low-frequency (30 kHz) low-dose ultrasound in the treatment of chronic venous leg ulcers, when added to conventional therapy of outpatients. Patients (n = 24) were randomized to conventional therapy with topical application of hydrocolloid dressings and compression therapy or conventional therapy with additional ultrasound treatment for 12 weeks. The ultrasound treatment consisted of 10-min of foot-bathing, with application of continuous ultrasound 100 mW/cm2 thrice-weekly. The ulcer area was measured by planimetry, using a millimeter grid before treatment and after 2, 4, 6, 8, 10 and 12 weeks of therapy. The ulcer radius and the daily ulcer radius reduction were calculated. Color photographs of the ulcers were taken under standard conditions at the same time. After each treatment, local findings and side effects were recorded. After 12 weeks of treatment the control group showed a mean decrease of 16.5 % in the ulcerated area. In contrast, the mean ulcerated area decreased by 55.4 % in the ultrasound group (p < 0.007). The daily ulcer reduction in the ultrasound-treated patients was 0.08 mm +/- 0.04 mm and in the placebo patients 0.03 mm +/- 0.03 mm. Patients recorded only minor side effects (e.g., a tingling feeling and occasionally pinhead-sized bleeding in the ulcer area). The authors concluded that the application of low-frequency and low-dose ultrasound is a helpful treatment option in chronic venous leg ulcers, especially if they do not respond to conventional ulcer treatment.
In a randomized, double-blinded, controlled, multi-center study, Ennis and colleagues (2005) examined the safety and effectiveness of MIST ultrasound therapy for the healing of recalcitrant diabetic foot ulcers. Patients (n = 55) received standard of care, which included products that provide a moist environment, off-loading diabetic shoes and socks, debridement, as well as wound evaluation and measurement. The "therapy" was either active 40 kHz ultrasound delivered by a saline mist or a "sham device" that delivered a saline mist without the use of ultrasound. After 12 weeks of care, the proportion of wounds healed (defined as complete epithelialization without drainage) in the active ultrasound therapy device group was significantly higher than that in the sham control group (40.7 % versus 14.3 %, p = 0.0366, Fisher's exact test). The ultrasound treatment was easy to use and no difference in the number and type of adverse events between the two treatment groups was noted. The authors concluded that compared to control, MIST ultrasound therapy was found to increase the healing rate of recalcitrant, diabetic foot ulcers. They noted that the findings of this study suggest the need for further research, including assessing the impact of quantitative biopsy results at enrollment, debridement depth and impact on healing, as well as the potential anti-microbial action of MIST ultrasound therapy.
In a non-comparative study, Ennis et al (2006) ascertained the incidence of wound closure for chronic non-healing lower extremity wounds of various etiologies using MIST ultrasound therapy. These investigators also determined the optimal treatment duration with this device, quantified end points that correlated with a maximal clinical response and identified potential synergistic therapies that could be used in conjunction with this therapy. Furthermore, they analyzed the impact of MIST ultrasound therapy on the microcirculatory flow patterns within the wound bed. A total of 23 patients were included in this study. Control data were obtained from a previously published, prospectively collected database. During an 8-month period, a total of 29 lower extremity wounds in the 23 subjects who met criteria for inclusion were treated with MIST ultrasound therapy. Standard of care was provided for 2 weeks for all wounds screened for the study. A failure to achieve an area reduction greater than 15 % qualified the patient for enrollment to the trial and the addition of MIST ultrasound therapy to the current treatment regimen. Main outcome measures were wound healing, area and volume reduction, and laser Doppler-derived mean voltage (a marker for microcirculatory flow). Overall, 69 % of the wounds in the study were healed using an intent-to-treat model. When MIST ultrasound was used as a stand-alone therapy, median time to healing was 7 weeks. Historic controls were healed with a median time to healing of 10 weeks; however, a statistically significant number of these patients required wound-related hospitalization and surgical procedures to achieve closure compared with the wounds in the present study. The authors concluded that treatment with MIST ultrasound achieved healing in chronic wounds when used as a stand-alone therapy or in combination with moist wound care in 69 % of cases. Response to low-frequency, non-contact ultrasound was evident within 4 weeks of therapy. Earlier transition to secondary procedures and decreased utilization of inpatient care might result in more cost-effective wound healing than the current standard of care. These researchers noted that a well-designed health economic-based clinical trial is needed to evaluate this technology.
In a prospective, randomized, controlled study, Kavros and co-workers (2007) assessed the clinical role of MIST ultrasound therapy in the treatment of non-healing leg and foot ulcers associated with chronic critical limb ischemia. Subjects included 35 patients who received MIST ultrasound therapy plus the standard of wound care (treatment group) and 35 patients who received the standard of wound care alone (control group). Standard of wound care alone or standard of wound care plus MIST ultrasound therapy were provided for 12 weeks or until wounds were fully healed. MIST ultrasound therapy was administered thrice-weekly for 5 minutes per treatment. Main outcome measure was percentage of patients with greater than 50 % reduction in wound size from the index measurement after 12 weeks of treatment. The relationship of transcutaneous oximetry pressure in the supine and dependent position was evaluated as a factor in assessing the potential to heal ischemic ulcerations of the foot and leg. A significantly higher percentage of patients treated with the standard of care plus MIST ultrasound therapy achieved greater than 50 % wound healing at 12 weeks than those treated with the standard of care alone (63 % versus 29 %; p < 0.001). Thus, failure to achieve the minimum wound healing requirement occurred in 37 % of patients in the treatment group and 71 % of patients in the control group. The predictive value of baseline transcutaneous oxygen pressure may benefit the clinician when assessing the potential to heal ischemic wounds. The authors concluded that the rate of healing of cutaneous foot and leg ulcerations in patients with chronic critical limb ischemia improved significantly when MIST ultrasound therapy was combined with the standard of wound care. It should be noted that although the study reported on the importance of baseline transcutaneous oxygen pressure on wound healing, patients with low (1 to 20 mm Hg) and high (21 to 40 mm Hg) transcutaneous oxygen pressure levels do not appear to be equally distributed between the groups.
Gehling and Samies (2007) noted that pain associated with chronic wounds and related wound care modalities presents a persistent clinical challenge in patient care, yet evidence supporting the effects of interventions on wound pain remains sparse. In response to initial clinical observations that several patients with painful chronic lower-extremity wounds reported a reduction in wound pain shortly after ultrasound therapy was initiated, a retrospective chart review and analysis of reported pain scores was conducted. The records of 15 consecutive patients (7 men and 8 women, age range of 28 to 88 years) with painful, non-healing, lower-extremity wounds treated for 2 to 4 weeks with MIST ultrasound therapy were reviewed and recorded pain scores abstracted. Mean pain scores decreased from 8.07 (+/- 1.91) pre-treatment to 1.67 (+/- 1.76) post-treatment (p = 0.0003). No patients reported worsening pain after treatment commenced. The authors concluded that this preliminary evidence suggests that prospective, controlled clinical studies to evaluate the effect of this treatment on wound-related pain are warranted.
In an open-label, non-randomized, baseline-controlled clinical case series, Kavros and Schenck (2007) conducted a feasibility study to characterize the effects of non-contact low-frequency ultrasound therapy for chronic, recalcitrant lower-leg and foot ulcerations. Patients were initially treated with the Mayo Clinic standard of care before the addition of or the switch to non-contact low-frequency ultrasound therapy. These researchers analyzed the medical records of 51 patients (median +/- SD age, 72 +/- 15 years) with one or more of the following conditions: diabetes mellitus, neuropathy, limb ischemia, chronic renal insufficiency, venous disease, and inflammatory connective tissue disease. All patients had lower-extremity ulcers, 20 % had a history of amputation, and 65 % had diabetes. Of all the wounds, 63 % had a multi-factorial etiology, and 65 % had associated transcutaneous oximetry levels below 30 mm Hg. The mean +/- SD treatment time of wounds during the baseline standard of care control period versus the non-contact low-frequency ultrasound therapy period was 9.8 +/- 5.5 weeks versus 5.5 +/- 2.8 weeks (p < 0.0001). Initial and end measurements were recorded, and percent volume reduction of the wound was calculated. The mean +/- SD percent volume reduction in the baseline standard of care control period versus the non-contact low-frequency ultrasound therapy period was 37.3 % +/- 18.6 % versus 94.9 % +/- 9.8 % (p < 0.0001). The authors concluded that the use of non-contact low-frequency ultrasound improved the rate of healing and closure in recalcitrant lower-extremity ulcerations. They also stated that further clinical and basic science investigations using this technology are warranted.
As stated earlier, there is no consensus regarding the effectiveness of ultrasound therapy in the management of chronic wounds. There exists randomized, controlled studies, meta-analysis, as well as clinical practice guidelines that question the value of this approach.
In a randomized, controlled trial, Lundeberg et al (1990) studied the effects of pulsed ultrasound in conjunction with a standard treatment for healing chronic leg ulcers on 44 patients. All patients received standard treatment (paste impregnated bandage and a self-adhesive elastic bandage) plus placebo-ultrasound or pulsed ultrasound (1:9, 0.5 Watt/cm2 at 1 mHz, for 10 min) thrice-weekly for 4 weeks, thereafter twice-weekly for 4 weeks and once-weekly for the following 4 weeks. Percentage healed ulcer area and comparison of percentage healed ulcers were examined after 4, 8 and 12 weeks. There were no significant differences in the proportion of healed ulcers or ulcer area in the pulsed ultrasound group as compared with the placebo group.
In another randomized, controlled study, Eriksson et al (1991) examined the effects of ultrasound in conjunction with standard treatment on healing chronic leg ulcers. A total of 38 patients were divided into two groups. All patients received standard treatment (paste impregnated bandage and a self-adhesive elastic bandage plus placebo ultrasound or ultrasound (1.0 Watt/cm2 at 1 mHz, for 10 mins) twice-weekly for 8 weeks. Percentage healed ulcer area and number of healed ulcers were compared after 2, 4, 6 and 8 weeks. There were no significant differences in the proportion of healed ulcers or ulcer area in the ultrasound group as compared with the placebo group.
In a meta-analysis on ultrasound therapy in the treatment of chronic leg ulceration, Johannsen et al (1998) concluded that available evidence would suggest that ultrasound has the best effect when delivered in low doses around the edge of the ulcer, but further studies are needed to confirm this possible effect and to assess a possible dose-response relationship.
In a Health Technology Assessment on wound care management, Cullum et al (2001) concluded that there is generally insufficient reliable evidence to draw conclusions regarding the contribution of laser therapy, therapeutic ultrasound, electrotherapy and electromagnetic therapy to chronic wound healing.
In a Cochrane review on therapeutic ultrasound for pressure ulcers, Baba-Akbari Sari and colleagues (2006) concluded that there is no evidence of benefit of ultrasound therapy in the treatment of pressure ulcers. However, the possibility of beneficial or harmful effect cannot be ruled out due to the small number of trials, some with methodological limitations and small numbers of participants. The authors noted that further research is needed.
Systematic evidence reviews of therapeutic ultrasound in BMJ Clinical Evidence have concluded that therapeutic ultrasound of pressure ulcers and venous leg ulcers are of "unknown effectiveness" (Nelson and Jones, 2007; Cullum and Petherick, 2007).
The American College of Foot and Ankle Surgeons' clinical practice guideline on diabetic foot disorders (Frykberg et al, 2006) noted that low-intensity pulsed ultrasound has been suggested as a useful adjunct in promoting healing of Charcot fractures. Although promising in theory, this approach has yet been conclusively proven effective through large, prospective, multi-center, randomized trials. Additionally, the American Society of Plastic Surgeons' evidence-based clinical practice guideline on chronic wounds of the lower extremity (2007) did not mention the use of ultrasound therapy as an option of treatment.
In a retrospective analysis, Kavros and colleagues (2008) assessed the clinical role of non-contact, low-frequency MIST ultrasound therapy in the treatment of chronic lower-extremity wounds. A total of 163 patients who received MIST therapy plus standard of care (treatment group) and 47 patients who received the standard of care alone (control group) were examined. All wounds in the control and treatment groups received the standard of wound care and were followed for 6 months. In the treatment group, MIST therapy was administered to wounds 3 times per week for 90 days or until healed. Main outcome measures included proportion of wounds healed and wound volume reduction. Rate of healing was also quantified using 1-way analysis of variance to determine the slope of the regression line from starting volume to ending volume, where a steeper slope indicates a faster healing rate. Outcomes were evaluated in all wounds and etiology-specific subgroups. A significantly greater percentage of wounds treated with MIST therapy and standard of care healed as compared with those treated with the standard of care alone (53 % versus 32 %; p = 0.009). The slope of the regression line in the MIST arm (1.4) was steeper than the slope in the control arm (0.22; p = 0.002), indicating a faster rate of healing in the MIST-treated wounds. The authors concluded that the rate of healing and complete closure of chronic wounds in patients improved significantly when MIST therapy was combined with standard wound care. They stated that the addition of MIST therapy to standard wound care appears to expedite healing of chronic wounds in the lower extremities; and further research on the healing impact of MIST therapy in specific wound type will provide additional clinical insight into the use of this non-contact, low-frequency ultrasound therapy.
There are also case studies as well as case-series studies on the use non-contact, low-frequency ultrasound in the management of various types of chronic wounds such as burns, digital ulcers, infected surgical wounds, and sacral pressure ulcers (Serena, 2008; Samies and Gehling, 2008; Fleming, 2008; Waldrop and Serfass, 2008; Liguori et al, 2008; Schmuckler, 2008; Howell-Taylor et al, 2008). Moreover, the majority of the authors concluded that additional studies (large, prospective, randomized trials) are needed to elucidate the role of non-contact, low-frequency ultrasound in the management of chronic wounds.
In a systematic review of the effectiveness of interventions to enhance the healing of chronic ulcers of the foot in diabetes, Hinchliffe and associates (2008) identified interventions for which there is evidence of effectiveness. A search was made for reports of the effectiveness of interventions assessed in terms of healing, ulcer area or amputation in controlled clinical studies published prior to December 2006. Methodological quality of selected studies was independently assessed by 2 reviewers using Scottish Intercollegiate Guidelines Network (SIGN) criteria. Selected studies fell into the following categories: sharp debridement and larvae; antiseptics and dressings; chronic wound resection; hyperbaric oxygen therapy (HBOT); reduction of tissue edema; skin grafts; electrical and magnetic stimulation and ultrasound. Heterogeneity of studies prevented pooled analysis of results. Of the 2,251 papers identified, 60 were selected for grading following full text review. Some evidence was found to support hydrogels as desloughing agents and to suggest that a systemic HBOT may be effective. Topical negative pressure may promote healing of post-operative wounds, and resection of neuropathic plantar ulcers may be beneficial. These researchers stated that more information was needed to confirm the effectiveness and cost-effectiveness of these and other interventions. No data were found to justify the use of any other topically applied product or dressing, including those with antiseptic properties. They noted that further evidence to substantiate the effect of interventions designed to enhance the healing of chronic ulcers is urgently needed. Until such evidence is available from robust trials, there is limited justification for the use of more expensive treatments and dressings.
In a systematic review on treatment of pressure ulcers, Reddy et al (2008) concluded that there is little evidence to support routine nutritional supplementation or adjunctive therapies including ultrasound compared with standard care. The review of randomized controlled clinical trials found no clear evidence for the effectivness of ultrasound in healing of pressure ulcers.
Busse et al (2009) determined the effectiveness of low-intensity pulsed ultrasonography (LIPUS) for healing of fractures. Electronic literature search without language restrictions of CINAHL, Embase, Medline, HealthSTAR, and the Cochrane Central Registry of Controlled Trials, from inception of the database to 10 September 2008 was carried out. Eligible studies were randomized controlled trials (RCTs) that enrolled patients with any kind of fracture and randomly assigned them to low intensity pulsed ultrasonography or to a control group. Two reviewers independently agreed on eligibility; 3 reviewers independently assessed methodological quality and extracted outcome data. All outcomes were included and meta-analyses done when possible. A total of 13 RCTs, of which 5 assessed outcomes of importance to patients, were included. Moderate quality evidence from 1 trial found no effect of LIPUS on functional recovery from conservatively managed fresh clavicle fractures; whereas low quality evidence from 3 trials suggested benefit in non-operatively managed fresh fractures (faster radiographic healing time mean 36.9 %, 95 % confidence interval [CI]: 25.6 % to 46.0 %). A single trial provided moderate quality evidence suggesting no effect of LIPUS on return to function among non-operatively treated stress fractures. Three trials provided very low quality evidence for accelerated functional improvement after distraction osteogenesis. One trial provided low quality evidence for a benefit of LIPUS in accelerating healing of established non-unions managed with bone graft. Four trials provided low quality evidence for acceleration of healing of operatively managed fresh fractures. The authors concluded that evidence for the effect of LIPUS on healing of fractures is moderate to very low in quality and provides conflicting results. Although overall results are promising, establishing the role of LIPUS in the management of fractures requires large, blinded trials, directly addressing patient important outcomes such as return to function.
An assessment by the Ontario Ministry of Health and Long Term Care, Medical Advisory Secretariat (MAS, 2009) concluded that the efficacy of ultrasound in improving complete closure of pressure ulcers has not been established. The review stated that there is no evidence of a benefit of using ultrasound therapy in the treatment of pressure ulcers and the possibility of a beneficial or harmful effect cannot be ruled out due to the very small number of trials.
In a Cochrane review, Cullum et al (2010) examined if ultrasound increases the healing of venous leg ulcers. These investigators searched the Cochrane Wounds Group Specialised Register (searched 24 February 2010); The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2010); Ovid MEDLINE (1950 to February Week 2 2010); In-Process & Other Non-Indexed Citations (searched 24 February 2010); Ovid EMBASE 1980 to 2010 Week 07; EBSCO CINAHL 1982 to 24 February 2010. Randomized controlled trials comparing ultrasound with no ultrasound were selected. Two authors independently assessed the search results and selected eligible studies. Details from included studies were summarized using a data extraction sheet, and double-checked. They tried to contact trial authors for missing data. A total of 8 trials were included; all had unclear, or high risks of bias, with differences in duration of follow-up, and ultrasound regimens. Six trials evaluated high-frequency ultrasound and 5 of these reported healing at 7 to 8 weeks. Significantly more patients healed with ultrasound than without it at 7 to 8 weeks (pooled RR 1.4, 95 % CI: 1.0 to 1.96), but later assessments at 12 weeks showed the increased risk of healing with ultrasound was no longer statistically significant (pooled RR 1.47, 95 % CI: 0.99 to 2.20). One poor-quality study of high-frequency ultrasound found no evidence of an effect on healing after 3 weeks' of treatment. Two trials evaluated low-frequency ultrasound and reported healing at different time points. Both trials reported no evidence of a difference in the proportion of ulcers healed with ultrasound compared with no ultrasound: both were significantly under-powered. The authors concluded that trials evaluating ultrasound for venous leg ulcers are small, poor-quality and heterogeneous. There is no reliable evidence that ultrasound hastens healing of venous ulcers. There is a small amount of weak evidence of increased healing with ultrasound, but this requires confirmation in larger, high-quality RCTs. There is no evidence of a benefit associated with low-frequency ultrasound.
An assessment of the MIST therapy system for the promotion of wound healing in chronic and acute wounds prepared for the National Institute for Clinical Excellence (NICE) (Batki et al, 2010) found "the manufacturer, Celleration, has on file over 200 publications on the MIST Therapy, which includes 104 unpublished single case studies held on Celleration patient registry and eight published case series in magazine "Thoughts on Therapy" funded by Celleration. The remainder of the publications consist of case series, posters and abstracts, and educational assessment of clinical uses on various wound etiology which the NICE assessment found to be not large enough to provide statistical outcome data". The assessment prepared for NICE found that a meta-analysis submitted by Celleration acknowledges limitations of the data, and noted that the Celleration meta-analysis stated that “first, all studies were either prospective or retrospective observational studies and are subject to the limitations inherent with non-randomised designs”. The NICE assessment stated, "however, the analysis is largely based on changes within patients, rather than comparison between groups, and is therefore of very little value". The assessment also found: "the main limitation is that there are only two small RCTs comparing MIST Therapy with no MIST Therapy. Moreover, duration of follow-up is generally inadequate with few reports on outcome beyond 9 weeks post treatment. Less serious issues consist of the limited range of ulcer types in the studies and failure to consider other promising new treatments apart from MIST .... ".
The final NICE's report on MIST therapy (2011) noted that the committee considered that the MIST Therapy system showed promise in the treatment of chronic wounds and its use was supported by expert opinion. The potential cost savings claimed for its use depend primarily on evidence of comparative effectiveness. The low-quality of that evidence and consequent uncertainty about its relative effectiveness in healing wounds compared with standard care alone meant that the case for routine adoption in the NHS could not be supported at the time of writing.
Gottrup and Apelqvist (2012) stated that management of foot ulcer in individuals with diabetes remains a major therapeutic challenge throughout the world. These investigators performed a critical review of evidence of present and new techniques and devices in the treatment of diabetic foot ulcer. The golden standard for optimal evidence in the Cochrane system is level I -- RCTs, and meta-analyses of several RCTs. Available evidence on different types of wound debridement; use of anti-microbials; use of dressings in wounds; topical negative pressure; hyperbaric oxygen treatment; electrical, electromagnetic, laser, shockwave, and ultrasound therapies; growth and cell biology factors; cell products and tissue engineering; bioengineered skin and skin grafts; and adjuvant therapies were evaluated. The results of this review showed that there is limited evidence on the highest level to justify a change in routine clinical practice. There is a paucity of high-quality evidence, because the studies were often based on inadequate sample size, short follow-up, non-random allocation to treatment arms, non-blinded assessment of outcomes, poor description of control, and concurrent intervention. The heterogeneity of the population (of both people and ulcers), with multiple factors contributing to both ulcer onset and failure to heal, makes the trial design difficult in this field. Another fundamental reason for the lack of evidence is the general use of the outcome measure “complete healing”. The authors concluded that when the results of this updated review were taken together with those of the earlier reports, they provided limited evidence to justify a change in routine clinical practice. For this reason, there is an urgent need to increase the quality of clinical studies. A re-evaluation of which type of research is acceptable for producing evidence in the wound area may be important in the future.
Game et al (2012) noted that the outcome of management of diabetic foot ulcers is poor, and there is continuing uncertainty concerning optimal approaches to management. It was for these reasons that in 2006 the International Working Group of the Diabetic Foot (IWGDF) working group on wound healing undertook a systematic review of the evidence to inform protocols for routine care and to highlight areas which should be considered for further study. The same working group has now updated this review by considering papers on the interventions to improve the healing of chronic ulcers published between December 2006 and June 2010. Methodological quality of selected studies was independently assessed by 2 reviewers using Scottish Intercollegiate Guidelines Network criteria. Selected studies fell into the following 10 categories: (i) sharp debridement and wound bed preparation with larvae and hydrotherapy; (ii) wound bed preparation using antiseptics, applications and dressing products; (iii) resection of the chronic wound; (iv) HBOT; (v) compression or negative pressure therapy; (vi) products designed to correct aspects of wound biochemistry and cell biology associated with impaired wound healing; (vii) application of cells, including platelets and stem cells; (viii) bioengineered skin and skin grafts; (ix) electrical, electromagnetic, lasers, shockwaves and ultrasound; and (x) other systemic therapies that did not fit in the above categories. Heterogeneity of studies prevented pooled analysis of results. Of the 1,322 papers identified, 43 were selected for grading following full text review. The present report was an update of the earlier IWGDF systematic review, but the conclusion was similar: that with the exception of HBOT and, possibly, negative pressure wound therapy, there is little published evidence to justify the use of newer therapies. This echoed the conclusion of a recent Cochrane review and the systematic review undertaken by the NICE Guidelines Committee in the United Kingdom. Analysis of evidence presented considerable difficulties in this field particularly as controlled studies are few and the majority are of poor methodological quality.
In summary, there is currently insufficient evidence to support the effectiveness of ultrasound therapy in the management of patients with chronic wounds.
|
Close Window
