Change In Ulcer Size Research Articles

Sub-ulcer Foam Sclerotherapy in Patients with Venous Leg Ulcer, Analysis and Technical Aspects of 134 Consecutive Patients.

For this retrospective study, we analyzed the sub-ulcer foam sclerotherapy technique in patients with venous leg ulcer (VLU). This study included 134 patients treated with sub-ulcer foam sclerotherapy at the Oulu University Hospital vascular outpatient clinic from January 2012 to December 2021. All included patients received sub-ulcer foam sclerotherapy as part of the treatment strategy for superficial venous insufficiency. Compression therapy and local wound care were organized for VLU treatment. A follow-up visit was scheduled for one month after the sub-ulcer foam sclerotherapy. Change in ulcer size, local (skin necrosis, infection) or systemic (deep vein thrombosis, pulmonary embolism) complications, and time to ulcer healing were monitored. The occurrence of major limb-related complications (amputation, surgical revision) was monitored for one year postoperatively. One month after sub-ulcer treatment, ulcers were smaller or completely healed in 108 (81%) patients. Ulcer healing was completed in 123 (92%) patients at one year and 131 (98%) patients at two years. Complications were recorded in four (3%) patients, three (2%) who were diagnosed with erysipelas requiring antibiotic treatment and one (1%) patient diagnosed with local dermatitis. During the one-year follow-up, no major limb-related complications (surgical revisions or amputations) arose. Sub-ulcer foam sclerotherapy may be a feasible addition to superficial vein reflux elimination in patients with VLU and a low risk for complications.

Angiogenic Precursor Cell Treatment of Critical Limb Ischemia Decreases Ulcer Size, Amputation and Death Rate: Re-Examination of phase II ACP NO-CLI Trial Data

Introduction: Critical limb ischemia has a prevalence in the US of 1.33%, with mortality 15-20% and major amputation 10-40% per year. Stem cell treatment has emerged as a treatment option for the 45% of patients for whom revascularization procedures are not possible. Objective: This study re-examines the data of the Phase II clinical treatment of no option Critical limb ischemia with Hemostemix’ angiogenic cell precursors, focusing upon ulcer wound healing, amputation and death rate of this cohort. Methods: Primary endpoints were changes in ulcer size and major amputation or death within one year of treatment. The secondary endpoint was change in pain level. Results: From 2015 to 2021, 67 patients with no option Critical limb ischemia were allocated to treatment with ACP-01 (46/67) or placebo (21/67). From this data, only patients who presented with wound ulcers before administration of ACP-01 were reviewed (21 treatment, 8 placebo). Ulcer size in the treated group decreased from a mean of 1.46 cm2 to 0.48 mm2 (p = 0.01) by 3 months. There was no significant decrease in the size of the ulcers of the placebo group (p < 0.54). At one year there were no complications related to treatment. The treatment group had one amputation (4.8%) and one death (4.8%); the placebo group had 2 amputations (25%) and 1 death (12.5%). Change in pain was not significant in either group at 3 months, but at 1 year was improved in the placebo group (p = 0.01). Conclusion: The administration of ACP-01 within a program of careful patient follow up is safe and associated with reduced ulcer size and decreased rate of amputation and death. Consideration should be given to re-administration of stem cell treatments every 3-6 months to optimize improvement of Critical limb ischemia. Further studies, more appropriately powered, are warranted.

Dressings and topical agents containing hyaluronic acid for chronic wound healing.

Dressings and topical agents containing hyaluronic acid for chronic wound healing.

Endovenous ablation for venous leg ulcers.

Venous leg ulcers (VLUs) are a serious manifestation of chronic venous disease affecting up to 3% of the adult population. This typically recalcitrant and recurring condition significantly impairs quality of life, and its treatment places a heavy financial burden upon healthcare systems. The longstanding mainstay treatment for VLUs is compression therapy. Surgical removal of incompetent veins reduces the risk of ulcer recurrence. However, open surgery is an unpopular option amongst people with VLU, and many people are unsuitable for it. The efficacy of the newer, minimally-invasive endovenous techniques has been established in uncomplicated superficial venous disease, and these techniques can also be used in the management of VLU. When used with compression, endovenous ablation aims to further reduce pressure in the veins of the leg, which may impact ulcer healing. To determine the effects of superficial endovenous ablation on the healing and recurrence of venous leg ulcers and the quality of life of people with venous ulcer disease. In April 2022 we searched the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE (including In-Process & Other Non-Indexed Citations); Ovid Embase and EBSCO CINAHL Plus. We also searched clinical trials registries for ongoing and unpublished studies, and scrutinised reference lists of relevant included studies as well as reviews, meta-analyses and health technology reports to identify additional studies. There were no restrictions on the language of publication, but there was a restriction on publication year from 1998 to April 2022 as superficial endovenous ablation is a comparatively new technology. Randomised controlled trials (RCTs) comparing endovenous ablative techniques with compression versus compression therapy alone for the treatment of VLU were eligible for inclusion. Studies needed to have assessed at least one of the following primary review outcomes related to objective measures of ulcer healing such as: proportion of ulcers healed at a given time point; time to complete healing; change in ulcer size; proportion of ulcers recurring over a given time period or at a specific point; or ulcer-free days. Secondary outcomes of interest were patient-reported quality of life, economic data and adverse events. Two reviewers independently assessed studies for eligibility, extracted data, carried out risk of bias assessment using the Cochrane RoB 1 tool, and assessed GRADE certainty of evidence. The previous version of this review found no RCTs meeting the inclusion criteria. In this update, we identified two eligible RCTs and included them in a meta-analysis. There was a total of 506 participants with an active VLU, with mean durations of 3.1 months ± 1.1 months in the EVRA trial and 60.5 months ± 96.4 months in the VUERT trial. Both trials randomised participants to endovenous treatment and compression or compression alone, however the compression alone group in the EVRA trial received deferred endovenous treatment (after ulcer healing or from six months). There is high-certainty evidence that combined endovenous ablation and compression compared with compression therapy alone, or compression with deferred endovenous treatment, improves time to complete ulcer healing (pooled hazard ratio (HR) 1.41, 95% CI 1.36 to 1.47; I2 = 0%; 2 studies, 466 participants). There is moderate-certainty evidence that the proportion of ulcers healed at 90 days is probably higher with combined endovenous ablation and compression compared with compression therapy alone or compression with deferred endovenous treatment (risk ratio (RR) 1.14, 95% CI 1.00 to 1.30; I2 = 0%; 2 studies, 466 participants). There is low-certainty evidence showing an unclear effect on ulcer recurrence at one year in people with healed ulcers with combined endovenous treatment and compression when compared with compression alone or compression with deferred endovenous treatment (RR 0.29, 95% CI 0.03 to 2.48; I2 = 78%; 2 studies, 460 participants). There is also low-certainty evidence that the median number of ulcer-free days at one year may not differ (306 (interquartile range (IQR) 240 to 328) days versus 278 (IQR 175 to 324) days) following combined endovenous treatment and compression when compared with compression and deferred endovenous treatment; (1 study, 450 participants). There is low-certainty evidence of an unclear effect in rates of thromboembolism between groups (RR 2.02, 95% CI 0.51 to 7.97; I2 = 78%, 2 studies, 506 participants). The addition of endovenous ablation to compression is probably cost-effective at one year (99% probability at GBP 20,000/QALY; 1 study; moderate-certainty evidence). Endovenous ablation of superficial venous incompetence in combination with compression improves leg ulcer healing when compared with compression alone. This conclusion is based on high-certainty evidence. There is moderate-certainty evidence to suggest that it is probably cost-effective at one year and low certainty evidence of unclear effects on recurrence and complications. Further research is needed to explore the additional benefit of endovenous ablation in ulcers of greater than six months duration and the optimal modality of endovenous ablation.

Negative pressure wound therapy for treating pressure ulcers.

Pressure ulcers, also known as bedsores, pressure sores, or pressure injuries, are localised damage to the skin and underlying soft tissue, usually caused by intense or long-term pressure, shear, or friction. Negative pressure wound therapy (NPWT) has been widely used in the treatment of pressure ulcers, but its effect needs to be further clarified. This is an update of a Cochrane Review first published in 2015. To evaluate the effectiveness of NPWT for treating adult with pressure ulcers in any care setting. On 13 January 2022, we searched the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE (including In-Process & Other Non-Indexed Citations); Ovid Embase, and EBSCO CINAHL Plus. We also searched ClinicalTrials.gov and the WHO ICTRP Search Portal for ongoing and unpublished studies and scanned reference lists of relevant included studies as well as reviews, meta-analyses, and health technology reports to identify additional studies. There were no restrictions with respect to language, date of publication, or study setting. We included published and unpublished randomised controlled trials (RCTs) comparing the effects of NPWT with alternative treatments or different types of NPWT in the treatment of adults with pressure ulcers (stage II or above). Two review authors independently conducted study selection, data extraction, risk of bias assessment using the Cochrane risk of bias tool, and the certainty of the evidence assessment using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) methodology. Any disagreement was resolved by discussion with a third review author. This review included eight RCTs with a total of 327 randomised participants. Six of the eight included studies were deemed to be at a high risk of bias in one or more risk of bias domains, and evidence for all outcomes of interest was deemed to be of very low certainty. Most studies had small sample sizes (range: 12 to 96, median: 37 participants). Five studies compared NPWT with dressings, but only one study reported usable primary outcome data (complete wound healing and adverse events). This study had only 12 participants and there were very few events; only one participant was healed in the study (risk ratio (RR) 3.00, 95% confidence interval (CI) 0.15 to 61.74, very low-certainly evidence). There was no evidence of a difference in the number of participants with adverse events in the NPWT group and the dressing group, but the evidence for this outcome was also assessed as very low certainty (RR 1.25, 95% CI 0.64 to 2.44, very low-certainty evidence). Changes in ulcer size, pressure ulcer severity, cost, and pressure ulcer scale for healing (PUSH) sores were also reported, but we were unable to draw conclusions due to the low certainly of the evidence. One study compared NPWT with a series of gel treatments, but this study provided no usable data. Another study compared NPWT with 'moist wound healing', which did not report primary outcome data. Changes in ulcer size and cost were reported in this study, but we assessed the evidence as being of very low certainty; One study compared NPWT combined with internet-plus home care with standard care, but no primary outcome data were reported. Changes in ulcer size, pain, and dressing change times were reported, but we also assessed the evidence as being of very low certainty. None of the included studies reported time to complete healing, health-related quality of life, wound infection, or wound recurrence. The efficacy, safety, and acceptability of NPWT in treating pressure ulcers compared to usual care are uncertain due to the lack of key data on complete wound healing, adverse events, time to complete healing, and cost-effectiveness. Compared with usual care, using NPWT may speed up the reduction of pressure ulcer size and severity of pressure ulcer, reduce pain, and dressing change times. Still, trials were small, poorly described, had short follow-up times, and with a high risk of bias; any conclusions drawn from the current evidence should be interpreted with considerable caution. In the future, high-quality research with large sample sizes and low risk of bias is still needed to further verify the efficacy, safety, and cost-effectiveness of NPWT in the treatment of pressure ulcers. Future researchers need to recognise the importance of complete and accurate reporting of clinically important outcomes such as the complete healing rate, healing time, and adverse events.

Hydrogel dressings for venous leg ulcers.

Venous leg ulcers are a chronic health problem that cause considerable economic impact and affect quality of life for those who have them. Primary wound contact dressings are usually applied to ulcers beneath compression therapy to aid healing, promote comfort and control exudate. There are numerous dressing products available for venous leg ulcers and hydrogel is often prescribed for this condition; however, the evidence base to guide dressing choice is sparse. To assess the effects of hydrogel wound dressings on the healing of venous leg ulcers in any care setting. In May 2021,we searched the Cochrane Wounds Specialised Register, CENTRAL, Ovid MEDLINE, Ovid Embase and EBSCO CINAHL Plus. We also searched clinical trials registries for ongoing and unpublished studies, and scanned reference lists of relevant included studies, reviews, meta-analyses and health technology reports to identify additional studies. There were no restrictions with respect to language, date of publication or study setting. We included randomised controlled trials (RCTs), either published or unpublished, that compared the effects of hydrogel dressing with other dressings on the healing of venous leg ulcers. We excluded trials evaluating hydrogel dressings impregnated with antimicrobial, antiseptic or analgesic agents as these interventions are evaluated in other Cochrane Reviews. We used standard methodological procedures expected by Cochrane. We assessed the certainty of the evidence using the GRADE approach. We included four RCTs (10 articles) in a qualitative analysis. Overall, 272 participants were randomised, in sample sizes ranging from 20 to 156 participants. The mean age of the included population in the trials ranged from 55 to 68 years, 37% were women based on studies that reported the sex of participants.The studies compared hydrogel dressings with the following: gauze and saline, alginate dressing, manuka honey and hydrocolloid. Two studies were multicentre and the others were single-centre trials. Length of treatment using hydrogel dressing was four weeks in three studies and two weeks in one study. The follow-up period was the same as the duration of treatment in three studies and in one study the follow-up for wound healing was at 12 weeks after four weeks of treatment. Overall risk of bias was high for all trials because at least one of the three key criteria (selection bias, detection bias and attrition bias) was at high risk. Hydrogel compared with gauze and saline It is uncertain whether there is a difference in complete wound healing (risk ratio (RR) 5.33, 95% confidence interval (CI) 1.73 to 16.42; 1 trial, 60 participants) or change in ulcer size (mean difference (MD) -1.50, 95% CI -1.86 to -1.14; 1 trial, 60 participants) between interventions because the certainty of the evidence is very low. Data reported from one trial were incomplete for time-to-ulcer healing. Hydrogel compared with alginate dressing It is uncertain whether there is a difference in change in ulcer size between hydrogel and alginate gel because the certainty of the evidence is very low (MD -41.80, 95% CI -63.95 to -19.65; 1 trial, 20 participants). Hydrogel compared with manuka honey It is uncertain whether there is a difference in complete wound healing (RR 0.75, 95% CI 0.46 to 1.21; 1 trial, 108 participants) or incidence of wound infection (RR 2.00, 95% CI 0.81 to 4.94; 1 trial, 108 participants) between interventions because the certainty of the evidence is very low. Hydrogel compared with hydrocolloid One study (84 participants) reported on change in ulcer size between hydrogel and hydrocolloid; however, further analysis was not possible because authors did not report standard errors or any other measurement of variance of a set of data from the means. Therefore, it is also uncertain whether there is a difference in change in ulcer size between hydrogel and hydrocolloid because the certainty of the evidence is very low. No studies provided evidence for the outcomes: recurrence of ulcer, health-related quality of life, pain and costs. Overall, independent of the comparison, the certainty of evidence is very low and downgraded twice due to risk of bias and once or twice due to imprecision for all comparisons and outcomes. There is inconclusive evidence to determine the effectiveness of hydrogel dressings compared with gauze and saline, alginate dressing, manuka honey or hydrocolloid on venous leg ulcer healing. Practitioners may, therefore, consider other characteristics such as costs and symptom management when choosing between dressings. Any future studies assessing the effects of hydrogel on venous wound healing should consider using all the steps from CONSORT, and consider key points such as appropriate sample size with the power to detect expected differences, appropriate outcomes (such as time-to-event analysis) and adverse effects. If time-to-event analysis is not used, at least a longer follow-up (e.g. 12 weeks and above) should be adopted. Future studies should also address important outcomes that the studies we included did not investigate, such as health-related quality of life, pain and wound recurrence.

Prognostication of Asymptomatic Penetrating Aortic Ulcers: A Modern Approach

Literature detailing the natural history of asymptomatic penetrating aortic ulcers (PAUs) is sparse and lacks long-term follow-up. This study sought to determine the rate of asymptomatic PAU growth over time and adverse events from asymptomatic PAU. A cohort of patients with asymptomatic PAU from 2005 to 2020 was followed. One ulcer was followed per patient. Primary end points were change in size over time and the composite of symptoms, radiographic progression, rupture, and intervention; cumulative incidence function estimated the incidence of the composite outcome. Ulcer size and rate of change were modeled using a linear mixed-effects model. Patient and anatomic factors were evaluated as potential predictors of the outcomes. There were 273 patients identified. The mean age was 75.5±9.6 years; 66.4% were male. The majority of ulcers were in the descending thoracic aorta (53.9%), followed by abdominal aorta (41.4%) and aortic arch (4.8%). Fusiform aneurysmal disease was present in 21.6% of patients at a separate location; 2.6% had an associated intramural hematoma; 23.6% had at least 1 other PAU. Symptoms developed in 1 patient who ruptured; 8 patients (2.9%) underwent an intervention for PAU (1 for rupture, 2 for radiographic progression, 5 for size/growth) at a median of 3.1 years (interquartile range, 1.0-6.5) after diagnosis. Five- and 10-year cumulative incidence of the primary outcome, adjusted for competing risk of death, was 3.6% (95% CI, 1.6%-6.9%) and 6.5% (95% CI, 3.1%-11.4%), respectively. For 191 patients with multiple computed tomography scans (760 total computed tomographies) with a median radiographic follow-up of 3.50 years (interquartile range, 1.20-6.63 years), mean initial ulcer width, ulcer depth, and total diameter were 13.6 mm, 8.5 mm, and 31.4 mm, respectively. A small but statistically significant change over time was observed for ulcer width (0.23 mm/y) and total diameter (0.24 mm/y); ulcer depth did not significantly change over time. Hypertension, hyperlipidemia, diabetes, initial ulcer width >20 mm, thrombosed PAU, and associated saccular aneurysm were associated with larger changes in ulcer size over time; however, the magnitude of difference was small, ranging from 0.4 to 1.9 mm/y. Asymptomatic PAU displayed minimal growth and infrequent complications including rupture. Asymptomatic PAU may be conservatively managed with serial imaging and risk factor modification.

447-P: The Efficacy and Safety Trial of ENERGI-F703 in Diabetic Wound Healing: A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Clinical Trial

Diabetic foot ulcers (DFUs) is a catastrophic ailment that exerts serious medical and psychological impact on diabetic patients. ENERGI-F703 is a hydrogel containing 0.02% adenine as a prodrug for the replenishment of cellular ATP levels to accelerate diabetic wound healing. To demonstrate its efficacy and safety in patients with DFU, 141 patients with type 2 diabetes (T2D) ≥ 20 years old with HbA1c 6.5-12 % and intractable DFUs (Wagner grade 1-3 without active osteomyelitis) were enrolled, randomized 2:1 ENERGI-F703 group (67.4%) to vehicle group (32.6%) for 12 weeks. Most target ulcers were grade 2 (63.6%, N=84) and located mainly on the foot sole (30.3%, N=40) or toe (27.3%, N=36). The primary endpoint was complete ulcer closure rate at the end of treatment. Secondary endpoints included the time required to complete ulcer closure, the accumulated confirmed ulcer closure rate and percentage change in ulcer size at each of the post-treatment visit, and adverse event incidence. Patients with confirmed complete ulcer closure were follow-up for additional 12 weeks and patients with incomplete ulcer closure were additional 4 weeks. An intend-to-treat (ITT) population of 132 subjects and a per-protocol (PP) population of 107 were included in efficacy analyses. Among the PP population with Wagner grade 1 or 2 target ulcers, we observed a significantly higher response rate in the ENERGI-F703 group compared to the vehicle group (48.0% vs. 20.8%, P = 0.0250). Among the ITT population, we also observed a higher response rate in the ENERGI-F703 group compared to the vehicle group (40.3% vs. 20.7%, P = 0.0656). Time to complete target ulcer closure was also faster among patients receiving ENERGI-F703 Gel in both the ITT population (P = 0.0380) and PP population (P = 0.0180). There were no suspected unexpected serious adverse reactions observed throughout the study. Our study showed that ENERGI-F703 Gel is an effective and well-tolerated treatment for DFU. Disclosure G. Young: Employee; Self; Energenesis Biomedical Co., Ltd. J. Lin: Employee; Self; Energenesis Biomedical Co., Ltd. Y. Cheng: Employee; Self; Energenesis Biomedical Co., Ltd. H. Chen: None. C. Huang: Employee; Self; Energenesis Biomedical Co., Ltd.

Topical oxygen therapy in the treatment of diabetic foot ulcers: a multicentre, open, randomised controlled clinical trial.

Perfusion and blood oxygen levels are frequently insufficient in patients with hard-to-heal wounds due to poor circulation, vascular disruption and vasoconstriction, reducing the wound's capacity to heal. This study aimed to investigate the effect of topical oxygen on healing rates in patients with hard-to-heal diabetic foot ulcers (DFUs) (i.e., non-responsive over four weeks). This multicentre, open-label, community-based randomised clinical trial compared standard care (SOC) with or without continuous topical oxygen therapy (TOT) for 12 weeks in patients with DFUs or minor amputation wounds. SOC included debridement, offloading with total contact casting (TCC) and appropriate moisture balance. Primary endpoints were the number of patients to achieve complete wound closure and percentage change in ulcer size. Secondary endpoints were pain levels and adverse events. For the study, 145 patients were randomised with index ulcers graded Infectious Diseases Society of America (IDSA) 1 or 2, or Wagner 1 or 2. In the intention-to-treat analysis, 18/64 (28.1%) patients healed in the SOC group at 12 weeks compared with 36/81 (44.4%) in the SOC plus TOT group (p=0.044). There was a statistically significant reduction in wound area between the groups: SOC group mean reduction: 40% (standard deviation (SD) 72.1); SOC plus TOT group mean reduction: 70% (SD 45.5); per protocol p=0.005). There were no significant differences in changes to pain levels or adverse events. This study suggests that the addition of TOT to SOC facilitates wound closure in patients with hard-to-heal DFUs.

Interventions for treating leg ulcers in people with sickle cell disease.

The frequency of skin ulceration makes an important contributor to the morbidity burden in people with sickle cell disease. Many treatment options are available to the healthcare professional, although it is uncertain which treatments have been assessed for effectiveness in people with sickle cell disease. This is an update of a previously published Cochrane Review. To assess the clinical effectiveness and harms of interventions for treating leg ulcers in people with sickle cell disease. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register. We searched LILACS (1982 to January 2020), ISI Web of Knowledge (1985 to January 2020), and the Clinical Trials Search Portal of the World Health Organization (January 2020). We checked the reference lists of all the trials identified. We also contacted those groups or individuals who may have completed relevant randomised trials in this area. Date of the last search of the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register: 13 January 2020; date of the last search of the Cochrane Wounds Group Trials Register: 17 February 2017. Randomised controlled trials of interventions for treating leg ulcers in people with sickle cell disease compared to placebo or an alternative treatment. Two authors independently selected studies for inclusion. All three authors independently assessed the risk of bias of the included studies and extracted data. We used GRADE to assess the quality of the evidence. Six studies met the inclusion criteria (198 participants with 250 ulcers). Each trial investigated a different intervention and within this review we have grouped these as systemic pharmaceutical interventions (L-cartinine, arginine butyrate, isoxsuprine) and topical pharmaceutical interventions (Solcoseryl® cream, arginine-glycine-aspartic acid (RGD) peptide dressing and topical antibiotics). No trials on non-pharmaceutical interventions were included in the review. All trials had an overall unclear or high risk of bias, and drug companies sponsored four of them. We were unable to pool findings due to the heterogeneity in outcome definitions, and inconsistency between the units of randomisation and analysis. Three interventions reported on the change in ulcer size (arginine butyrate, RGD peptide, L-cartinine). Of these, only arginine butyrate showed a reduction of ulcer size compared with a control group, mean reduction -5.10 cm² (95% CI -9.65 to -0.55), but we are uncertain whether this reduces ulcer size compared to standard care alone as the certainty of the evidence has been assessed as very low. Three trials reported on complete leg ulcer closure (isoxsuprine, arginine butyrate, RGD peptide matrix; very low quality of evidence). None reported a clinical benefit. No trial reported on: the time to complete ulcer healing; ulcer-free survival following treatment for sickle cell leg ulcers; quality of life measures; incidence of amputation or harms. Given the very low quality of the evidence identified in this updated Cochrane Review we are uncertain whether any of the assessed pharmaceutical interventions reduce ulcer size or result in leg ulcer closure in treated participants compared to controls. However, this intervention was assessed as having a high risk of bias due to inadequacies in the single trial report. Other included studies were also assessed as having an unclear or high risk of bias. The harm profile of the all interventions remains inconclusive.

Evaluation of the effectiveness of a healing gel on ulcer management- A clinical case study

Objective: To evaluate the clinical efficacy, and safety of a healing oral gel containing hyaluronic acid, CPC and lignocaine as active ingredients in the management of oral ulcers. Materials and Methods: The healing oral gel was evaluated in 10 subjects during a 7 day daily application in the mouth. Clinical efficacy was investigated in the form of changes in ulcer size, pain intensity, erythema, and exudation at days 0, 3 and 7 of study inclusion. Results: There was upto 86 % reduction in erythema, 88% reduction in ulcer size and upto 100% reduction seen with regard to pain intensity and exudation. Conclusion: The hyaluronic acid based gel proved to be effective in topical management of ulcers. It was also found to be was superior in decreasing ulcer size, erythema, and exudation. Also brought faster healing in ulcers. Keywords: Gel, Hyaluronic Acid, Oral ulcer.

N-acetylcysteine versus chlorhexidine in treatment of aphthous ulcers: a preliminary clinical trial

Introduction This study sought to assess the efficacy of N-acetyl cysteine (NAC) in the treatment of recurrent aphthous stomatitis (RAS). Methods Fifty-eight patients, aged 28 ± 9.7 years, presented with clinically diagnosed RAS to two oral medicine centers. They were assigned randomly to a single application of either NAC (200 mg dissolved in water, n = 38) or 0.12% chlorhexidine digluconate (CHX, n = 20) mouthwashes for 30 seconds. Pain was measured using a Visual Analog Scale (VAS). The size of the ulcer was measured through its greatest dimension using a periodontal probe. These two measurements were taken pre-application (day 1) and 2nd, 4th, and 6th day post-application. Average time (in days) until complete healing was assessed. Results Of all participants, 33 (57%) were females; 34 (59%) married; 29 (50%) reported a family history of aphthae; and 51 (88%) were affected with minor RAS. There were greater improvement in pain from day 1 with NAC on the second day (−3.0 ± 2.0 versus −1.8 ± 1.9; p = .028) and on the fourth day (−5.0 ± 2.6 versus −3.4 ± 2.7; p = .041). The differences with regard to the change in ulcer size and average healing time were not significant between NAC and CHX. Conclusion Single application of NAC results in a clinically significant reduction of RAS-associated pain within one day of application and is more effective than CHX.

Allogeneic keratinocyte for intractable chronic diabetic foot ulcers: A prospective observational study.

Chronic diabetic foot ulcers (DFUs) are a common problem in patients with diabetes and are often difficult to treat. The application of newly developed dressing material in patients with chronic DFUs has been reported to be effective. The purpose of this study was to evaluate the usefulness of allogeneic keratinocyte treatment for chronic DFUs. We performed weekly allogeneic keratinocyte treatment for up to 12 weeks in 71 patients with intractable DFUs. We investigated healing rate, wound-healing velocity, and time to 50% wound size reduction and analysed factors affecting ulcer healing. Fifty-six patients (78.8%) had complete wound healing. Forty-six patients (64.7%) showed complete healing within an average of 6.1 weeks, and 10 patients (14.1%) showed partial healing with an average 35.5% reduction vs initial size at the end of follow up. The 10 patients who showed partial healing continued to receive treatment after the 12-week study period. The mean time to complete wound healing was 7.8 weeks. Fifteen patients (21.1%) experienced treatment failure because of infection, local necrosis, no change in ulcer size, or osteomyelitis during the follow-up period. No adverse events were observed. Allogeneic keratinocyte treatment is effective for chronic, difficult-to-treat DFUs.

Corneal Debridement Combined with Intrastromal Voriconazole for Recalcitrant Fungal Keratitis.

Background To analyze the therapeutic effects of corneal debridement combined with intrastromal voriconazole in recalcitrant fungal keratitis. Methods This is a retrospective study. Fourteen patients with recalcitrant fungal keratitis were treated by corneal debridement combined with intrastromal voriconazole (50 μg/0.1 ml). This paper reviews and analyzes the patients' basic state, surgical intervention, medicinal treatment, and outcomes. Results The mean sizes of infiltration and ulcer were (5.54 ± 1.32)mm and (3.46 ± 1.03)mm, respectively, and the mean depth was (315.43 ± 57.72)μm. Twelve of the patients had satellite lesion, and 2 suffered hypopyon. After intrastromal voriconazole, the size of infiltration decreased significantly to (4.32 ± 1.10)mm (P < 0.001), but there was no significant change in ulcer size ((3.36 ± 0.92)mm, P = 0.082). Thirteen patients were cured after corneal debridement. The mean healing time was (15.38 ± 7.38) days. Excluding one cured patient with optic nerve atrophy and one patient for whom the treatment failed, the mean best-corrected visual acuity after healing was (0.23 ± 0.18)LogMAR, a significant improvement compared to pretreatment (0.87 ± 0.57(LogMAR), P = 0.01). The mean corneal astigmatism was (1.3 ± 1.6)D of 12 cured patients after healing and (1.0 ± 0.7)D at final follow-up, and there was no significant difference (P = 0.374). Conclusions Corneal debridement combined with intrastromal voriconazole is a secure and effective treatment for recalcitrant fungal keratitis.

Phototherapy for treating foot ulcers in people with diabetes.

Foot ulcers are a disabling complication of diabetes that affect 15% to 25% of people with diabetes at some time in their lives. Phototherapy is a relatively new, non-invasive, and pain-free treatment method, which promotes the ulcer repair process through multiple mechanisms such as increased cell growth and vascular activity. Phototherapy may be used as an alternative approach for the treatment of foot ulcers in people with diabetes, but the evidence for its effect compared with placebo or other treatments has not yet been established. To assess the effects of phototherapy for the treatment of foot ulcers in people with diabetes. We searched the Cochrane Wounds Specialised Register (11 October 2016), the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, 2016, Issue 10), Ovid MEDLINE (11 October 2016), Ovid MEDLINE (In-Process & Other Non-Indexed Citations) (11 October 2016), Ovid Embase (11 October 2016), EBSCO CINAHL Plus (11 October 2016), and China National Knowledge Infrastructure (24 June 2017). We also searched clinical trials registries for ongoing and unpublished studies on 24 June 2017, and screened reference lists to identify additional studies. We used no restrictions with respect to language, date of publication, or study setting. Randomised controlled trials or cluster randomised controlled trials that 1) compared phototherapy with sham phototherapy, no phototherapy, or other physical therapy modalities, 2) compared different forms of phototherapy, or 3) compared phototherapy of different output power, wavelength, power density, or dose range, in adults with diabetes and an open foot ulcer of any severity, in any setting. Two review authors independently performed study selection, data extraction, and 'Risk of bias' assessment. We combined the study outcomes when appropriate. Eight trials with 316 participants met the inclusion criteria. Most of the included studies were single-centre studies that were carried out in clinics or hospitals with a sample size ranging from 14 to 84. We generally considered the included studies to be at unclear or high risk of bias, as they had one domain at high risk of bias, or three or more domains at unclear risk of bias.We did not identify any studies that reported valid data for time to complete wound healing. Meta-analysis of four studies including 116 participants indicated that participants receiving phototherapy may experience a greater proportion of wounds completely healed during follow-up compared with those receiving no phototherapy/placebo (64.5% for the phototherapy group versus 37.0% for the no phototherapy/placebo group; risk ratio 1.57, 95% confidence interval 1.08 to 2.28; low-quality evidence, downgraded for study limitations and imprecision). Two studies mentioned adverse events in the results; one study with 16 participants suggested that there were no device-related adverse events, and the other study with 14 participants suggested that there was no clear difference between phototherapy and placebo group.Four studies reported change in ulcer size, but primarily due to high heterogeneity, they were not combined. Results from individual trials (including 16 participants to 84 participants) generally suggested that after two to four weeks of treatment phototherapy may result in a greater reduction in ulcer size but the quality of the evidence was low due to unclear risk of bias in the original trial and small sample size. We based the analyses for quality of life and amputations on only one study each (28 participants and 23 participants respectively); both outcomes showed no clear difference between the phototherapy group and the no phototherapy/placebo group. This systematic review of randomised trials suggested that phototherapy, when compared to no phototherapy/placebo, may increase the proportion of wounds completely healed during follow-up and may reduce wound size in people with diabetes, but there was no evidence that phototherapy improves quality of life. Due to the small sample size and methodological flaws in the original trials, the quality of the evidence was low, which reduces our confidence in these results. Large, well-designed randomised controlled trials are needed to confirm whether phototherapy could be an effective option for the treatment of foot ulcers in people with diabetes.

Therapeutic ultrasound for venous leg ulcers.

Venous leg ulcers are a type of chronic, recurring, complex wound that is more common in people aged over 65 years. Venous ulcers pose a significant burden to patients and healthcare systems. While compression therapy (such as bandages or stockings) is an effective first-line treatment, ultrasound may have a role to play in healing venous ulcers. To determine whether venous leg ulcers treated with ultrasound heal more quickly than those not treated with ultrasound. We searched the Cochrane Wounds Specialised Register (searched 19 September 2016); the Cochrane Central Register of Controlled Trials (CENTRAL; the Cochrane Library 2016, Issue 8); Ovid MEDLINE (including In-Process & Other Non-Indexed Citations, MEDLINE Daily and Epub Ahead of Print) (1946 to 19 September 2016); Ovid Embase (1974 to 19 September 2016); and EBSCO CINAHL Plus (1937 to 19 September 2016). We also searched three clinical trials registries and the references of included studies and relevant systematic reviews. There were no restrictions based on language, date of publication or study setting. Randomised controlled trials (RCTs) that compared ultrasound with no ultrasound. Eligible non-ultrasound comparator treatments included usual care, sham ultrasound and alternative leg ulcer treatments. Two authors independently assessed the search results and selected eligible studies. Details from included studies were summarised using a data extraction sheet, and double-checked. We attempted to contact trial authors for missing data. Eleven trials are included in this update; 10 of these we judged to be at an unclear or high risk of bias. The trials were clinically heterogeneous with differences in duration of follow-up, and ultrasound regimens. Nine trials evaluated high frequency ultrasound; seven studies provided data for ulcers healed and two provided data on change in ulcer size only. Two trials evaluated low frequency ultrasound and both reported ulcers healed data.It is uncertain whether high frequency ultrasound affects the proportion of ulcers healed compared with no ultrasound at any of the time points evaluated: at seven to eight weeks (RR 1.21, 95% CI 0.86 to 1.71; 6 trials, 678 participants; low quality evidence - downgraded once for risk of bias and once for imprecision); at 12 weeks (RR 1.26, 95% CI 0.92 to 1.73; 3 trials, 489 participants; moderate quality evidence - downgraded once for imprecision); and at 12 months (RR 0.93, 95% CI 0.73 to 1.18; 1 trial, 337 participants; low quality evidence - downgraded once for unclear risk of bias and once for imprecision).One trial (92 participants) reported that a greater percentage reduction in ulcer area was achieved at four weeks with high-frequency ultrasound, while another (73 participants) reported no clear difference in change in ulcer size at seven weeks. We downgraded the level of this evidence to very low, mainly for risk of bias (typically lack of blinded outcome assessment and attrition) and imprecision.Data from one trial (337 participants) suggest that high frequency ultrasound may increase the risk of non-serious adverse events (RR 1.29, 95% CI 1.02 to 1.64; moderate quality evidence - downgraded once for imprecision) and serious adverse events (RR 1.21, 95% CI 0.78 to 1.89; moderate quality evidence downgraded once for imprecision).It is uncertain whether low frequency ultrasound affects venous ulcer healing at eight and 12 weeks (RR 3.91, 95% CI 0.47 to 32.85; 2 trials, 61 participants; very low quality evidence (downgraded for risk of bias and imprecision)).High-frequency ultrasound probably makes little or no difference to quality of life (moderate quality evidence, downgraded for imprecision). The outcomes of adverse effects, quality of life and cost were not reported for low-frequency ultrasound treatment. It is uncertain whether therapeutic ultrasound (either high or low frequency) improves the healing of venous leg ulcers. We rated most of the evidence as low or very low quality due to risk of bias and imprecision.

A Study of Amniotic Membrane Graft in Treatment of Chronic Venous Leg Ulcers

Aim: To evaluate the efficacy of Amniotic Membrane graft in the treatment of chronic venous leg ulcers. Research Design and Methods: Prospective, randomized, non-blinded study. Eligible patients were randomized to one of 2 groups: Group I: (Control group) included 11 chronic leg ulcers, in which ulcers were treated with conventional moist wound dressings and multilayer compressive bandages. Group II: (Amniotic Membrane group) included 14 leg ulcers. Amniotic membrane was placed in contact with ulcer and held in place with secondary dressing and multilayer compressive bandages. all patients were evaluated for healing rate and change in ulcer size. Results: Healing rate showed significant difference between group I and group II (p = 0.001). Group II (AM) patients demonstrated near complete healing of 14 ulcers in 14-60 days with mean of 33.3 ± 14.7, healing rate range was 0.064- 2.22 and mean of 0.896 ± 0.646 cm2/day with 94% reduction in ulcer size. Taken AM grafts were seen in 28.6% (n=4) of group II. Reduction in ulcer size in taken AM graft was 94.7%, while 93% in non-taken AM graft. Conclusions: Our results suggest that using AM in treat leg ulcers not responding to conventional multilayer compression in patients with non- option chronic venous insufficiency.

Supervised exercise training as an adjunctive therapy for venous leg ulcers: study protocol for a randomised controlled trial.

BackgroundVenous leg ulcers are common, chronic wounds that are painful and reduce quality of life. Compression therapy is known to assist in the healing of venous leg ulceration. Supervised exercise training that targets an improvement in calf muscle pump function might be a useful adjunctive therapy for enhancing ulcer healing and other aspects of physical and mental health. However, the evidence of exercise for individuals with venous ulcers is sparse. Here, we describe the protocol for a study that aims to assess the feasibility of undertaking a randomised controlled trial of a supervised exercise programme in people who are receiving compression for venous ulceration.Methods/DesignThis is a randomised, controlled, assessor-blinded, two-centre, feasibility trial with two parallel groups. Eighty adults who are receiving lower-limb compression for a venous leg ulcer will be randomly assigned to receive usual care (compression only) or usual care plus a 12-week supervised exercise programme. Participants in the exercise group will be invited to undertake three, 60-minute sessions of supervised exercise each week, and each session will involve a combination of treadmill walking, upright cycling and strength and flexibility exercises for the lower limbs. Participants will be assessed before randomisation and 3, 6 and 12 months after randomisation. Primary outcomes include rates of recruitment, retention and adherence. Secondary outcomes include time to ulcer healing, proportion of participants healed, percentage and absolute change in ulcer size, health-related quality of life (EQ-5D-5L and VEINES-QOL/Sym), lower-limb cutaneous microvascular function (laser Doppler flowmetry coupled with iontophoresis) and physical fitness (30-second sit-to-stand test, chair sit and reach test, 6-minute walk test and ankle range of motion). The costs associated with the exercise programme and health-care utilisation will be calculated. We will also complete interviews with a sub-sample of participants to explore their experiences of having a venous ulcer and the acceptability of the exercise intervention and study procedures.DiscussionData from this study will be used to refine the supervised exercise programme, investigate the acceptability of the intervention and study design and determine the most appropriate outcome measures, thereby providing estimates of the factors needed to design an adequately powered trial across several centres.Trial registrationCurrent Controlled Trials, ISRCTN10205425 (May 2014) - http://www.controlled-trials.com/ISRCTN10205425 Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-015-0963-z) contains supplementary material, which is available to authorized users.

Wound cleansing for treating venous leg ulcers

Wound cleansing for treating venous leg ulcers

Interventions for treating leg ulcers in people with sickle cell disease.

The frequency of skin ulceration makes it an important contributor to the morbidity burden in people with sickle cell disease. Many treatment options are available to the healthcare professional, although it is uncertain which treatments have been assessed for effectiveness in people with sickle cell disease. To assess the clinical effectiveness and safety of interventions for treating leg ulcers in people with sickle cell disease. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register.We searched LILACS (1982 to August 2012), the African Index Medicus (up to August 2012), ISI Web of Knowledge (1985 to August 2012), and the Clinical Trials Search Portal of the World Health Organization (August 2012). We checked the reference lists of all the trials identified. We also contacted those groups or individuals who may have completed relevant randomised trials in this area.Date of the last search of the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register: 21 July 2014; date of the last search of the Cochrane Wounds Group Trials Register: 18 September 2014. Randomised controlled trials of interventions for treating leg ulcers in people with sickle cell disease compared to placebo or an alternative treatment. Two authors independently selected studies for inclusion. All three authors independently assessed the risk of bias of the included studies and extracted data. Six studies met the inclusion criteria (198 participants with 250 ulcers). Each trial investigated a different intervention and within this review we have grouped these as systemic pharmaceutical interventions (L-cartinine, arginine butyrate, isoxsuprine) and topical pharmaceutical interventions (Solcoseryl(®) cream, RGD peptide dressing, topical antibiotics). Three interventions reported on the change in ulcer size (arginine butyrate, RGD peptide, L-cartinine). Of these, RGD peptide matrix significantly reduced ulcer size compared with a control group, mean reduction 6.60cm(2) (95% CI 5.51 to 7.69; very low quality of evidence). Three trials reported on the incidence of complete closure (isoxsuprine, arginine butyrate, RGD peptide matrix; ranging between low and very low quality of evidence). None reported a significant effect. No trial reported on: the time to complete ulcer healing; ulcer-free survival following treatment for sickle cell leg ulcers; quality of life measures; or incidence of amputation. There was no reported information on the safety of these interventions. There is evidence that a topical intervention (RGD peptide matrix) reduced ulcer size in treated participants compared to controls. This evidence of efficacy is limited by the generally high risk of bias associated with these reports.We planned to analyse results according to general groups: pharmaceutical interventions (systemic and topical); and non-pharmaceutical interventions (surgical and non-surgical). However, we were unable to pool findings due to the heterogeneity in outcome definitions, and inconsistency between the unit of randomisation and the unit of analysis. This heterogeneity, along with a paucity of identified trials, prevented us performing any meta-analyses.This Cochrane review provides some evidence for the effectiveness of one topical intervention - RGD peptide matrix. However, this intervention was assessed as having a high risk of bias due to inadequacies in the single trial report. Other included studies were also assessed as having a high risk of bias. We recommend that readers interpret the trial results with caution. The safety profile of the all interventions was inconclusive.