Efficacy and safety of extracorporeal shock wave therapy for acute and chronic soft tissue wounds: A systematic review and meta‐analysis

This study aimed to evaluate and compare the effects of extracorporeal shock wave therapy (ESWT) and conventional wound therapy (CWT) for acute and chronic soft tissue wounds. All English‐language articles on ESWT for acute and chronic soft tissue wounds indexed in PubMed, Medline, Embase, Cochrane Central Register of Controlled Trials, Cochrane Library, Physiotherapy Evidence Database, and HealthSTAR published prior to June 2017 were included, as well as corresponding articles cited in reference lists of related review articles. The methodological quality of the selected studies was assessed with the Cochrane Collaboration''s “risk of bias” tool. Study design, subject demographics, wound aetiology, treatment protocols, assessment indexes, and follow‐up duration were extracted. The fixed or random‐effects model was used to calculate the pooled effect sizes according to studies’ heterogeneity. Ten randomised controlled trials (RCTs) involving 473 patients were included in this systematic review and meta‐analysis. The meta‐analysis showed that ESWT statistically significantly increased the healing rate of acute and chronic soft tissue wounds 2.73‐fold (odds ratio, OR = 3.73, 95% confidence interval, CI: 2.30‐6.04, P < .001) and improved wound‐healing area percentage by 30.45% (Standardized Mean Difference (SMD) = 30.45; 95% CI: 23.79‐37.12; P < .001). ESWT reduced wound‐healing time by 3 days (SMD = −2.86, 95% CI:‐3.78 to −1.95, P < .001) for acute soft tissue wounds and 19 days (SMD = −19.11, 95% CI: −23.74 to −14.47, P < .001) for chronic soft tissue wounds and the risk of wound infection by 53% (OR = 0.47, 95% CI: 0.24‐0.92, P = .03) when compared with CWT alone. Serious adverse effects were not reported. ESWT showed better therapeutic effects on acute and chronic soft tissue wounds compared with CWT alone. However, higher‐quality and well‐controlled RCTs are needed to further assess the role of ESWT for acute and chronic soft tissue wounds.     

Hyaluronic acid derivatives and their healing effect on burns,epithelial surgical wounds,and chronic wounds: A systematic review and meta‐analysis of randomized controlled trials

Hyaluronic acid (HA) is a polysaccharide common to most species and is found in many sites in the human body, including the skin and soft tissue. A systematic review of the literature and meta‐analysis was performed to identify randomized controlled trials, evaluating the use of HA derivatives in healing burns, epithelial surgical, and chronic wounds. Nine studies were identified, which met the search criteria and clinical endpoints of complete healing and percent wound size reduction when using HA vs. either an active or passive comparator. It was found in the vast majority of randomized controlled trials (eight of nine) that HA derivatives significantly improved the healing of wounds vs. traditional therapies or placebo (either via complete healing or a significant reduction in wound size) occurring from burns, venous insufficiency, diabetes, neuropathic insufficiency, and surgical removal of the epithelial layer (for tattoo removal). In the other remaining trial, one formulation of HA was compared with another, with the higher concentration showing improved application characteristics. Further, it was found in a meta‐analysis in subsets of patients with diabetic foot ulcers (neuropathic) that HA derivatives healed these types of wounds significantly faster than standard of care. These studies in aggregate show that HA derivatives accelerate the healing process in burns, epithelial surgical wounds, and chronic wounds.     

Metalloproteinases in chronic and acute wounds: A systematic review and meta‐analysis

A systematic review and meta‐analysis were undertaken in order to explore the influence of matrix metalloproteinases and their diagnostic methods in chronic and acute wounds. Searches were conducted in the PubMed (Medline) and Embase (Elsevier) databases from inception to late November 2017. We included clinical trials enrolling patients with cutaneous chronic and acute wounds where a validated diagnostic method was employed for metalloproteinases. We excluded in vitro, animal or preclinical studies, nonoriginal articles, and studies without available data for analysis. In addition, references of narrative and systematic reviews were scrutinized for additional articles. Eight studies met the inclusion criteria. Results revealed that the most frequently determined matrix metalloproteinases were MMP‐2 and MMP‐9, and were found in 54.5% of wounds. MMP‐9 was present in more than 50% of the chronic wounds with a range from 37 to 78%. However, metalloproteinases were found in only 20% of acute wounds, and other types of metalloproteinases were also observed (MMP‐2 and MMP‐3). On the basis of the available evidence, high levels of metalloproteinases have been correlated with significantly delayed wound healing in wounds of a variety of etiologies.     

Debridement of chronic wounds: a qualitative systematic review of randomized controlled trials

This article reviews the current evidence available regarding wound debridement of chronic wounds and collates data from existing randomized controlled trials.     

Efficacy of low‐level light therapy for improving healing of diabetic foot ulcers: A systematic review and meta‐analysis of randomized controlled trials

Diabetic foot ulcers are prevalent among patients with diabetes and negatively affect mortality and life expectancy. This study aimed to synthesize and systematically review the best evidence to assess the efficacy of low‐level light therapy in improving healing of diabetic foot ulcers. We search CINAHL, Cochrane Library, EMBASE, ProQuest, PubMed, Scopus, and Web of Science from inception until September 30, 2019. Meta‐analysis was performed using the Comprehensive Meta‐analysis 3.0 software. Overall effect was measured using Hedges' g and determined using the Z‐statistic at a significance level of P < .05. Heterogeneity was assessed using χ² and I² statistics. Twelve randomized controlled trials were included. Meta‐analysis revealed that 30.90% of the ulcer area was significantly reduced in the therapy group compared with the control group (Z = 3.95, P < .001) with a very large effect (g = 2.81). A 4.2 cm² reduction of the ulcer area was observed in the therapy group compared with the control group (Z = 2.17, P = .03) with a very large effect (g = 1.37). In addition, diabetic foot ulcers in the therapy group was 4.65 times more likely to heal completely than those in the control group (Z = 3.02, P = .003). Low‐level light therapy accelerates wound healing and reduces the size of diabetic foot ulcers. However, our review does not allow any recommendation for the best treatment parameters required to achieve improved healing. Future trials need to include a good design and large sample size in defining the optimal treatment parameters for ulcers of different sizes.     

Botulinum toxin injection vs topical nitrates for chronic anal fissure: an updated systematic review and meta‐analysis of randomized controlled trials

Aim

Chronic anal fissures (CAFs) are frequently encountered in coloproctology clinics. Chemical sphincterotomy with pharmacological agents is recommended as first‐line therapy. Topical nitrates (TN) heal CAF effectively but recurrences are common. An alternative treatment modality is injection of botulinum toxin (BT) into the anal sphincter. We aimed to perform an updated systematic review and meta‐analysis to compare the effectiveness of BT and TN in the management of CAF.

Method

PubMed, EMBASE and Cochrane databases were searched for relevant articles from inception until March 2017. All randomized controlled trials (RCTs) that reported direct comparisons of BT and TN were included. Two independent reviewers performed methodological assessment and data extraction. Random effects models were used to calculate pooled effect size estimates.

Results

Six RCTs describing 393 patients (194 BT, 199 TN) were included. There was significant heterogeneity among the trials. On random effects analysis there were no significant differences in incomplete fissure healing (OR = 0.47, 95% CI 0.13–1.68, P = 0.24) or recurrence (OR = 0.70, 95% CI 0.39–1.25, P = 0.22) between BT and TN, respectively. BT was associated with a higher rate of transient anal incontinence (OR = 2.53, 95% CI 0.98–6.57, P = 0.06) but significantly fewer total side effects (OR = 0.12, 95% CI 0.02–0.63, P = 0.01) and headache (OR = 0.10, 95% CI 0.02–0.60, P = 0.01) compared with TN.

Conclusion

BT is associated with fewer side effects than TN but there is no difference in fissure healing or recurrence. Patients need to be warned regarding the risk of transient anal incontinence associated with BT.     

Efficacy of topical insulin in wound healing: A preliminary systematic review and meta‐analysis of randomized controlled trials

Topical insulin has been shown to promote wound healing in various studies. Considering the absence of a systematic review and quantitative synthesis on the same, the present study was carried out. Using an appropriate search strategy, electronic databases were searched for randomized controlled trials that have compared topical application of insulin in wounds with normal saline. Standardize mean differences were calculated for the following outcome measures: healing rate of ulcers/wound, percent granulation tissue growth, microvessel density, time to heal, wound area and ulcer severity score. Cochrane's risk of bias tool was used for each of the studies and RevMan 5.3 software was used to generate the pooled estimates and Forest plots. The quality of evidence was assessed by the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) working group approach. A total of 8 studies were found eligible to be included in this review and 7 for the meta‐analysis. The pooled estimates were as follows: healing rate—0.04 [?1.38, 1.46]; percent granulation tissue—10.99 [?10.07, 32.06], microvessel density—3.01 [?1.67, 7.69] and wound area—?6.59 [?9.7, ?3.48]. There was only one study for each of the following outcome measures: time to heal and ulcer severity score. Hence, pooling of the results was not attempted for these outcome measures. The studies conducted in this field were preliminary and it was difficult to draw any conclusion regarding the use of insulin topically for wound healing.     

Adjunctive virtual reality for procedural pain management of burn patients during dressing change or physical therapy: A systematic review and meta‐analysis of randomized controlled trials

Dressing change and physical therapy are extremely painful procedures for burn patients. Adjunctive virtual reality therapy reportedly reduces pain when added to analgesics, but a summary analysis of the data has yet to be performed. We conducted this systematic review and meta‐analysis of randomized controlled trials to verify the pain‐reducing efficacy of virtual reality among burn patients undergoing dressing change or physical therapy. We searched MEDLINE (via PubMed), EMBASE (via OVID), and the Cochrane Central Register of Controlled Trials (via OVID) for relevant trials based on predetermined eligibility criteria from database establishment to February 2018. Two reviewers screened citations and extracted data independently. The quality of the included studies was evaluated according to the Cochrane Handbook, whereas statistical heterogeneity was assessed using chi‐square tests and I² statistics. Review Manager 5.3 was used for statistical analysis. Thirteen randomized controlled trials with 362 patients who underwent 627 burn dressing change or physical therapy sessions were included. The additional use of virtual reality significantly reduced pain intensity, time spent thinking about pain, and unpleasantness, and was more fun compared with that of using analgesics alone. Virtual reality is an effective pain reduction measurement added to analgesics for burn patients undergoing dressing change or physical therapy. However, multicenter, parallel group design randomized controlled trials are still required.     

Light‐emitting diodes in dermatology: A systematic review of randomized controlled trials

Objective

In dermatology, patient and physician adoption of light‐emitting diode (LED) medical technology continues to grow as research indicates that LEDs may be used to treat skin conditions. The goal of this systematic review is to critically analyze published randomized controlled trials (RCTs) and provide evidence‐based recommendations on the therapeutic uses of LEDs in dermatology based on published efficacy and safety data.

Methods

A systematic review of the published literature on the use of LED treatments for skin conditions was performed on September 13th 2017.

Results

Thirty‐one original RCTs were suitable for review.

Conclusions

LEDs represent an emerging modality to alter skin biology and change the paradigm of managing skin conditions. Acne vulgaris, herpes simplex and zoster, and acute wound healing received grade of recommendation B. Other skin conditions received grade of recommendation C or D. Limitations of some studies include small patient sample sizes (n < 20), absent blinding, no sham placebo, and varied treatment parameters. Due to few incidences of adverse events, affordability, and encouraging clinical results, we recommend that physicians use LEDs in clinical practice and researchers continue to explore the use of LEDs to treat skin conditions. Lasers Surg. Med. 50:613–628, 2018. © 2018 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.     

Human amniotic membrane allograft,a novel treatment for chronic diabetic foot ulcers: A systematic review and meta‐analysis of randomised controlled trials

To evaluate the efficacy and safety of human amniotic membrane (HAM) allograft in treating chronic diabetic foot ulcers (DFUs), a comprehensive search of randomised controlled trials in MEDLINE, EMBASE, PubMed, CENTRAL and Web of Science was conducted to December 7, 2019. Two reviewers independently screened the studies, extracted data, and evaluated the quality of studies. The primary outcome was the proportion of complete healing. The secondary outcomes were mean time to complete healing and adverse events. Statistical analyses were performed using RevMan 5.3. We identified 257 articles, of which 7 articles (465 participants) were included in the meta‐analysis. The proportion of complete wound healing in HAM plus standard of care (SOC) group was 3.88 times as high as that in SOC alone (RR: 3.88 [95% CI: 2.34, 6.44]) at 6 weeks, and 2.01 times at 12 weeks (RR: 2.01 [95%CI: 1.45, 2.77]). The intervention group had a significantly shorter time to complete healing (MD: −30.33 days, [95% CI: −37.95, −22.72]). The number needed to treat within 6 weeks was 2.3 ([95% CI: 1.8, 3.1]). No significant difference was shown in adverse events. Results were consistent in a sensitivity analysis. Hence, HAM plus SOC is effective and safe in treating chronic DFUs.     

Effect of bisphosphonates on bone mineral density in liver transplant patients: a meta‐analysis and systematic review of randomized controlled trials

Bone mineral density (BMD) loss after liver transplantation (LT) results in considerable morbidity with the increased risk of fractures. Data on the efficacy of bisphosphonate use in post LT patients is scarce. This meta‐analysis aims to summarize the results from published randomized controlled trials (RCTs) on the topic of interest. Electronic databases were searched to identify relevant publications. A total of 157 articles were identified and reviewed. Individual authors were contacted from relevant RCTs to obtain individual patient data where necessary to uniformly quantify BMD values post LT pre‐ and post LT. A total of six RCTs were used for final data extraction. (i) Lumbar Spine: In 364 patients (six studies, 182 in intervention and control groups each), bisphosphonate therapy improved BMD by 0.03 g/cm² (95% C.I. 0.01–0.05 g/cm²; P = 0.02) at 12 months post LT. (ii) Femoral neck: In 268 patients (four studies, 130 bisphosphonate, 138 control), bisphosphonate use did not result in a statistically significant change in BMD at the end of 1 year. None of the studies noted serious adverse effects related to bisphosphonate administration. Data on incident fractures could not be pooled because of heterogeneity. Bisphosphonate therapy during the first year in LT recipients appears to reduce accelerated bone loss and improve bone mineral density at the lumbar spine.     

Efficacy of topical silicone gel in scar management: A systematic review and meta‐analysis of randomised controlled trials

To assess the efficacy of topical silicone gel in the management of scars, we conducted this meta‐analysis. The systematic search was performed on PubMed, Web of Science and Embase, and six randomised controlled trials with a total of 375 patients were involved. The outcome data of Vancouver Scar Scale were extracted from the studies and their effect sizes were calculated using Review Manager 5.3. As a result, topical silicone gel significantly reduced pigmentation, height, and pliability scores postoperatively compared with placebos or no treatment (Pigmentation: standard mean difference [SMD] = −0.55 [−0.83 to –0.26], P = .0002; Height: SMD = −0.73 [−1.02 to –0.44], P < .00001; Pliability: SMD = −0.49 [−0.95 to –0.03], P = .04). Topical silicone gel and silicone gel sheet were comparably effective (P > .05). The performance of topical silicone gel and other non‐silicone topical treatment was also similar (P > .05). In summary, topical silicone gel was effective in post‐operative scar prevention.     

A systematic review of randomized controlled trials of wound dressings for chronic venous ulcer

OBJECTIVE: To determine whether more "modern" complex wound dressings further improve the healing of venous ulcers over that with simple wound dressings, we conducted a systematic review of randomized controlled trials (RCTs) of wound dressing trials that were published from October 1, 1997, through September 1, 2005. METHODS: We searched MEDLINE, CINAHL, and the Cochrane Controlled Trials Registry Database to identify RCTs. Criteria for ultimate selection included treatment with compression and an objective outcome describing the proportion of wounds healed. Twenty RCTs were identified that satisfied these criteria and were classified into three wound dressing classes: semiocclusive/occlusive group (n = 8), growth factor group (n = 7), and human skin equivalent group (n = 5). RESULTS: Assessment of study design quality for the 20 RCTs showed a low percentage (<49%) of RCTs that incorporated at least 3 of 7 indicators of trial quality, but it seemed better in the 5 RCTs that showed significance for ulcer healing; 4 of the studies used at least 6 of the 7 characteristics of adequate study design. Five (25%) of the 20 RCTs had a statistically significantly improved proportion of ulcers healed in the experimental dressing group over control values: zinc oxide paste bandage (79% vs 56%) and Tegasorb (59% vs 15%) in the semiocclusive/occlusive group and perilesional injection of granulocyte-macrophage colony-stimulating factor (57% vs 19%) and porcine collagen derived from small-intestine submucosa (Oasis; 55% vs 34%) in the growth factor group. In the sole significant RCT from the human skin equivalent group, Apligraf (63%) was superior to Tegapore (48%). Four of these five studies also showed an improved time to complete healing by Kaplan-Meier estimate. CONCLUSIONS: Certain wound dressings can improve both the proportion of ulcers healed and the time to healing over that achieved with adequate compression and a simple wound dressing. The selection of a specific dressing, however, will depend on the dressing characteristics for ease of application, patient comfort, wound drainage absorption, and expense.     

Negative pressure wound therapy for burn patients: A meta‐analysis and systematic review

Negative pressure wound therapy (NPWT), which has been applied in various medical specialties to accelerate wound healing, has been the object of a few investigations. We explored the effectiveness of NPWT and the possibility of its inclusion in burn management guidelines. Randomised controlled trials comparing NPWT with non‐NPWT treatments for burn wounds were extracted from PubMed. For the risk of bias analysis, all included studies were evaluated according to the Cochrane risk of bias tool and the approaches outlined in the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) Handbook. Outcomes such as graft take rate in the first week, infection rate, and overall complication rate were analysed. Six studies that included a total of 701 patients met our inclusion criteria. Qualitative analysis revealed that the NPWT group had a significantly better overall graft rate in the first week (P = 0.001) and a significantly lower infection rate (P = 0.04). No significant difference in the overall complication rate was found. Our results indicate that NPWT is a safe method for stimulating healing and lowering the infection rate of burn wounds. NPWT can be part of general burn management, and its incorporation into burn treatment guidelines is recommended.