Abstract
Background
Despite advances in wound care, the dressing and management of chronic ulcers on lower limbs remains unsatisfactory. The simplicity, cost effectiveness, and diverse application possibilities of ultrasound-guided foam sclerotherapy make it an attractive and effective approach to treat patients with no access to or contraindications to more invasive methods. We sought to evaluate the healing rate of chronic venous ulcers (Clinical, Etiological, Anatomical, Pathophysiological [CEAP] C6) in patients treated with ultrasound guided foam sclerotherapy.
Methods
From January 2018 to December 2020, 279 patients (336 legs) classified at the first consultation as stage 6 for CEAP disease were followed during treatment of axial venous reflux in saphenous and tributary veins with polidocanol (Aethosxysklerol) foam and evaluated at 52 weeks for complete healing rates or ≥50% ulcer size reduction, using Kaplan-Meier statistics and Cox regression to study the influence of covariates.
Results
The average age of the 279 patients was 55 years. Of these, 156 (56%) showed complete healing in 52 weeks and 89 (32%) achieved a wound area reduction of >50%. Ulcer size, severity, lymphedema, and reduced dorsiflexion of the ankle were significantly associated with healing difficulty. Time of ulcer progression up to beginning of treatment (P < .01), ulcer size (P = .01), lymphedema (P = .006), reduced dorsiflexion of the ankle (P = .01), and age ≥65 years (P = .003) were significantly associated with difficulty in healing. Patients with a mean Venous Clinical Severity Score of 18.7 had a better prognosis (18.7 vs 22.5; P < .001).
Conclusions
Most patients with chronic venous ulcers (CEAP 6) treated with foam sclerotherapy achieved healing or significant improvement within 52 weeks. Healing was highly influenced by time until treatment, ulcer size, reduced dorsiflexion of the ankle and/or lymphedema presence, and the use of compression therapy.
Keywords: Varicose ulcer, Ulcer, Venous hypertension, Sclerotherapy, Foam, Ultrasound, Doppler
Article Highlights.
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Type of Research: Retrospective analysis of prospectively collected registry data
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Key Findings: In 279 public health service patients with Clinical, Etiological, Anatomical, Pathophysiological stage 6 disease, whose axial venous reflux was treated with polidocanol foam, 56% had complete healing at 52 weeks and 32% had >50% wound area decrease. Difficulty in healing was associated significantly with ulcer progression, ulcer size, lymphedema, limited ankle mobility, and age ≥65 years (P < .01).
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Take Home Message: Most public health service patients with Clinical, Etiological, Anatomical, Pathophysiological 6 venous ulcers treated with foam sclerotherapy healed or improved significantly within 52 weeks. Healing was strongly influenced by the duration of ulcer, ulcer size, limited ankle mobility, lymphedema, and compression therapy use. Although these patients showed increased social vulnerability, it was possible to obtain high healing rates in a public health service with foam application.
Chronic venous ulcers are the most advanced stage of the venous disease on the lower limbs, resulting from venous insufficiency of varicose veins, venous obstruction, and subsequent venous hypertension. Chronic venous ulcers constitute an area of discontinuity of the epidermis and dermis, located between the knee and the ankle, usually on the medial side of the limb, persisting for 4 to 6 weeks or longer.1 Venous ulcers are the most common cause of ulcers in the lower limbs, accounting for 70% to 80% of all ulcers.2,3 Venous ulcers have a prolonged course and frequent recurrences, which impacts the patient's quality of life with a prevalence ranging from 0.2% to 1.0% of the total population and ≤5% of individuals >65 years old,4,5 affecting >2.2 million people in Europe and >6 million individuals in the United States.5 The more severe form of chronic venous insufficiency with active or healed ulcer was present in 3.6% of the patients (2.3% of men and 4.0% of women) in Brazil.6 Venous ulcers of the lower limbs greatly impact public health spending, corresponding with 1% to 2% of annual health expenditure in the United States and Western European countries,2,5,7 reaching the mark of $14 billion per year.3 The costs associated with venous ulcer treatment exceed $15,000, but increase significantly to >$34,000 per patient per year when the ulcer has a prolonged course.3 In addition to physical morbidity, there are psychosocial and emotional effects such as social isolation, loss of self-esteem, anxiety, depression, dependence, sleep disorders, and loss of the ability to work.5,7
Open surgical treatment, such as ligation, stripping, and stab phlebectomy for patients with severe forms of chronic venous insufficiency can be difficult owing to changes inherent to the disease, such as lipodermatosclerosis and eczema, advanced age, or associated comorbidities. Venous ablation methods such as ultrasound-guided foam sclerotherapy7,8 led to reduced morbidity compared with surgery, reducing postoperative pain, promoting rapid recovery, and reducing complication rates.9
The Brazilian public health system (Sistema Único de Saúde) provides free care to all Brazilian citizens. It offers only two treatment options for venous insufficiency: ultrasound-guided foam and surgery with saphenectomy and phlebectomies. Our study evaluated the efficacy of foam treatment in a public institution for patients with lower socioeconomic status and therefore with fewer opportunities to access wound care and prompt treatment, belonging to one of the poorest regions in Brazil. Bahia is in 22nd place among the 27 Brazilian states regarding the human development index and its average monthly income is $220.
Methods
From 2018 to 2020, 3708 patients were selected from the state public reference center for vascular and advanced venous diseases and treated with ultrasound guided foam sclerotherapy. Of these, 490 had chronic venous insufficiency in its most advanced stage, classified as Clinical, Etiological, Anatomical, Pathophysiological (CEAP) 6, but only 279 patients, in a total of 336 legs, met the inclusion criteria (Fig 1). Patients who did not attend clinic visits every 4 months for follow-up or retreatment sessions and a minimum of three visits in a 12-month period were considered lost to follow-up. The study was approved by the hospital's Research Ethics Committee (CAAE 40000920.3000000145) and an informed consent form was signed by all patients before the first treatment session. Patients were evaluated considering ulcer etiology; clinical data; comorbidities, such as peripheral arterial hypertension and diabetes mellitus; heart disease, such as coronary artery disease; valvular heart disease or arrhythmias; dyslipidemia (total cholesterol >200 mg/dL); smoking; obesity; and chronic peripheral arterial disease, denoting the presence of distal pulses, in addition to clinical changes such as dermatitis, pain, edema, and trophic changes in the skin. Afterward, they underwent a new vascular ultrasound examination with Doppler to define the therapeutic strategy. All patients who presented reflux (>0.5 seconds) in the superficial or perforating veins in the trunk or tributary system underwent sclerotherapy with polidocanol (POL) foam (Aethoxyclerol). Because there is important interobserver and intraobserver variation and inherent physiological variations that do not directly influence ulcer healing, the caliber of the saphenous veins was not validated in this sample. Wound extent was measured using a millimeter ruler. Reflux pattern was evaluated to determine the involvement of the veins, whether great or small saphenous veins, perforators, or only in tributaries. The number of sessions to heal the ulcer and the number of visits within the study period were computed. Ulcer healing was defined in the study as complete epithelialization of the wound. Patients aged from 18 to 85 years with advanced venous disease as defined by CEAP stage 6, a previous venous duplex scan, and who signed the informed consent form were considered eligible for the study. In the study, the ulcer diameter classification was based on the Venous Clinical Severity Score (VCSS), with mild indicating small, superficial ulcer (usually <2 cm in diameter); moderate denoting moderate-sized ulcers (2-6 cm in diameter) with some depth, potentially extending into subcutaneous tissue; and severe encompassing large (>6 cm in diameter) ulcers.1 Patients with peripheral arterial obstructive disease, acute or late deep venous thrombosis without satisfactory recanalization, pregnancy, thrombophilia, systemic infection, a history of allergy to POL, and refusal to sign the consent form were excluded. After completing the foam session, patients were instructed to continue using inelastic or elastic bandages, depending on the extent of the wound.
Fig 1.
Flow diagram of patients with venous leg ulcers (VLUs). CEAP, Clinical, Etiological, Anatomical, Pathophysiological.
Description of the service's routine for treating patients with foam
After clinical evaluation and ultrasound examination in an orthostatic position with a duplex scan, patients were placed in the supine position if the treatment objective was the great saphenous vein, accessory vein, or tributaries and perforator on the anterior surface, and prone position if the vein to be treated was the small saphenous vein or tributaries on the posterior surface. The veins were cannulated with a 26G scalp needle, 18G needle in the great or small saphenous veins, or a 25 × 8 needle with an extender. The sclerosing agent used was POL in concentrations of 1% and 3% in a proportion of 1 to 4 mL of room air,10, 11, 12 making up volumes that varied from 5 to 15 mL. The concentration was chosen based on the vein caliber, with a diameter of 8 mm as a cut-off point according to the 2014 European Guidelines for foam sclerotherapy,13 considering for veins with a caliber of ≥8 mm the use of POL 3%. Using Doppler ultrasound examination, the foam is visible as it is injected via puncture into the treated vein, minimizing the unwanted effects of vein extravasation and ensuring that the volume necessary to obliterate the vessel is reached. After the injection, patients were asked to dorsiflex the ankle while the vein path was subjected to extrinsic compression with bandages. After the dressing, patients received bandages or elastic stockings and walked for 20 minutes. They remained in compression bandages for 24 hours and were advised to return for follow-up in 7 days. All patients were evaluated with ultrasound examination in an upright position in relation to the superficial, deep and perforator venous systems, using the portable Mindray device/transducer with 7 to 12 MHz. Identification of the veins to be treated was made in mode B—gray scale and hemodynamic characterization of the reflux—spectral mode. Patients were evaluated 7 days after the first injection. If retreatment was necessary, the visits were scheduled 15 days thereafter. Patients were retreated at every visit in which additional reflux was seen until the ulcer healed completely or until no untreated vein was found. When treatment sessions were not performed, patients were reviewed at 3-month intervals until month 12.
During return visits, patietns were asked about adverse effects, including local pain and phlebitis. The ulcer and lower limbs were examined, and the duplex scan was repeated to look for possible deep vein thrombosis, confirmation of venous obliteration and its extent and presence of recanalization. Venous occlusion was confirmed by incompressibility and absence of flow.
Statistical analysis
Data spreadsheets were first input into Excel (Microsoft, Redmond, WA) and later transferred to the SPSS 18.0 electronic system. Quantitative variables were presented as means and standard deviation or median and interquartile range. The mean age was used to describe the sample. Age and estrogen are linked to chronic venous disease. The rationale for dividing the sample into three categories was: <50 years of age (nonmenopause), 50 to 64 (menopause and intermediate age) and ≥65, both exposures present. Once the normal distribution was determined, parametric tests were performed. Qualitative variables were described as absolute and relative frequencies with a 5% significance level. The healing rate at 52 weeks was assessed individually and variables with a P value of <.05 were analyzed together using Cox's regression.
Results
A total of 279 patients were selected from the foam outpatient clinic with a history of chronic venous ulcers classified as CEAP 6, with a total of 336 legs, from January 2018 to December 2020 (Fig 1). Of these, most were women (68.2%), with average age of 55.0 years. The ankle-brachial index was >0.7 in all participants. Most individuals had a primary reflux in the venous system (95.8%) rather than a disease of secondary etiology. Demographic data and comorbidities are listed in Table I.
Table I.
Characteristics of patients according to venous leg ulcer (VLU) status
| Characteristic | Healing status at 52 weeks |
||
|---|---|---|---|
| Healed (n = 156) | Not healed (n = 123) | P value | |
| Age, years | 55.2 ± 12.3 | 58.1 ± 11.7 | <.05 |
| Female sex | 101 (64.7) | 89 (72.4) | .18 |
| Nonsmokers | 143 (91.7) | 109 (88.6) | .39 |
| Comorbidity | |||
| Obesity | 56 (35.9) | 53 (43.1) | .22 |
| Hypertension | 69 (44.2) | 65 (52.8) | .15 |
| Type 2 diabetes | 18 (11.5) | 24 (19.5) | .06 |
| Heart disease | 5 (3.2) | 9 (7.3) | .12 |
| Dyslipidemia | 14 (9.0) | 15 (12.2) | .38 |
Cardiovascular risk factors include hypertenion and diabetes.
Values are mean ± standard deviation or number (%).
A single ulcer was present in 80.0% of patients at inclusion, 66 (24%) being mild, 118 (42%) moderate, and 95 (34%) severe. Regarding the evolution time, 168 (60%) were <6 months old. The frequencies of POL use, ultrasound-guided treatment, treated veins, and use of compression therapy are shown in Table II. Regardless of the vein (great or small saphenous, or tributary vein) that was treated, the results were similar (P = .57).
Table II.
Treated veins and treatment according to venous leg ulcer (VLU) status if totally healed or not at 52 weeks of follow-up
| Characteristic | Healing status at 52 weeks |
||||
|---|---|---|---|---|---|
| Healed (n = 156) | Non-healed (n = 123) | P value | |||
| Treated veins | |||||
| GSV | 86 | (55.5) | 59 | (48.4) | .57 |
| SSV | 4 | (2.6) | 5 | (4.1) | |
| Tributary veins | 30 | (19.4) | 28 | (23.0) | |
| GSV + SSV | 9 | (5.8) | 13 | (10.7) | |
| GSV + SSV + tributaries | 3 | (1.9) | 2 | (1.6) | |
| GSV + tributaries | 18 | (11.6) | 12 | (9.8) | |
| Type of treatment | |||||
| POL foam 1% | 123 | (79.4) | 107 | (87.0) | .17 |
| POL foam 3% | 29 | (18.7) | 13 | (10.6) | |
| Both (Pol. 1% & 3%) | 3 | (1.9) | 3 | (2.4) | |
| Compression therapy | 145 | (92.9) | 63 | (51.2) | <.05 |
GSV, Great saphenous vein; POL, polidocanol foam; SSV, short saphenous vein.
Values are number (%).
At 52 weeks, 156 patients (56.9%) had a fully healed ulcer and 89 (32.0%) showed a reduced wound area by >50%. The mean number of visits was 8.9 in 52 weeks. The number of treatments provided per patient was 5.2. The mean number of interventions to heal the ulcer was 2.7 and to correct all refluxes was 5.6. Considering a 1-year period of observation, 88.9% of the patients had healed or decreased ulcer area by 50%. We can show these numbers using the Kaplan-Meier curve analysis (Fig 2).
Fig 2.
Ulcer healing rates (cured and more than 50% healed). ∗At week 52, 31.9% of patients with ≥50% ulcer healing were classified as treatment partial success.
Men and women healed at a similar rate (61.8% vs 53.2%, respectively; P = .21). Patients with obesity showed a slightly lower healing rate than nonobese patients, but without statistical significance (P = .19). Healing was associated significantly with the time of ulcer evolution (P < .001), presence of reduced dorsiflexion of the ankle (P < .001), severity of the injury (P < .001), and lymphedema (P = .006) (Fig 3).
Fig 3.
Ulcer healing history >6 months.
In patients with severe ulcers, only 17 (10.9%) achieved complete healing. Seventeen patients (6.1%) had circumferential ulcers and only 1 of them healed within 36 months. Patients with unilateral ulcers healed more than bilateral ones (P < .001).
One hundred forty-five patients (52.0%) had isolated reflux of the great saphenous vein, 9 patients (3%) in the small saphenous vein and 59 (21.1%) only in tributary veins. The remaining participants had a combination of affected veins. Of the patients treated with reflux in the great saphenous vein, 86 (59.3%) healed completely and 36 (24.8%) reduced the ulcer by >50%. In those who treated the great and small saphenous veins, nine (5.8%) achieved complete lesion resolution.
For those treated with compression therapy, 69.7% healed and 27.9% reduced the size of the ulcer by >50%. Among those who did not use compression correctly, only 15.5% healed.
Hypertension, obesity, and diabetes had the worst rate of wound closure in 52 weeks, corresponding respectively to 48.5%, 48.6%, and 57.1%, respectively, of those who showed little or no evolution during the study period. Ulcer behavior varied according to age groups, evolving unfavorably in individuals over 65 years old (P = .003) (Fig 4). When comparing age with ulcer evolution time and ulcer size, we observed that the different strata showed similar evolution (P = .023).
Fig 4.
Cumulative ulcer complete healing up to 52 weeks of follow-up by age strata.
Patients who had a mild or moderate ulcer diameter showed a better healing rate than those classified as severe (P = .05). Throughout the treatment, patients showed an apparent improvement in each component of the VCSS score (difference in pretreatment and post-treatment score of 9.3; P = .24). Patients with an average VCSS of 18.7 had better healing rates. Patients with VCSS of >22.5 had a worse prognosis (Table III).
Table III.
Ulcer characteristics and Venous Clinical Severity Score (VCSS) ulcer grade
| Ulcer characteristics | Healing status at 52 weeks |
||
|---|---|---|---|
| Yes |
No |
P value | |
| All patients (n = 156) | All patients (n = 123) | ||
| Presence of | |||
| Stasis dermatitis by 4 range CEAP | 80 (51.3) | 77 (62.6) | .06 |
| Erysipelas | 3 (1.9) | 6 (4.9) | .17 |
| Leg edema | 130 (83.3) | 113 (91.9) | <.05 |
| Lymphedema | 4 (2.6) | 14 (11.4) | <.05 |
| Trophic changes of skin | 81 (51.9) | 90 (73.2) | <.05 |
| Post-thrombotic syndrome | 4 (2.6) | 2 (1.6) | .59 |
| Reduced dorsiflexion of the ankle | 3 (1.9) | 74 (60.2) | <.05 |
| Ulcer history >6 months | 24 (15.4) | 87 (70.7) | <.05 |
| Unilateral leg | 135 (86.5) | 88 (71.5) | <.05 |
| Circumferential ulcer | 0 (0.0) | 17 (13.8) | <.05 |
| VCSS | |||
| Ulcer grade | |||
| Mild | 54 (34.6) | 12 (9.8) | <.05 |
| Moderate | 85 (54.5) | 32 (26.0) | |
| Severe | 17 (10.9) | 79 (64.2) | |
| Intervention points | |||
| Preintervention | 19 (16-20) | 24 (20-25) | <.05 |
| Postintervention | 9 (7-11) | 16 (11-19) | <.05 |
| Difference by preintervention and postintervention | 9.3 ± 3.0 | 7.3 ± 3.4 | <.05 |
CEAP, Clinical, Etiological, Anatomical, Pathophysiological.
Values are number (%), median (range), or mean ± standard deviation.
Discussion
The ESCHAR study (Comparison of Open Surgical Treatment and Compression with Compression Alone in Chronic Venous Ulceration)14 reinforced the importance of treating varicose veins with compression and surgery, thus reducing venous hypertension and achieving better healing and a lower recurrence rate. In comparing compression alone and compression and surgery, the study showed that surgical correction of superficial venous reflux provides a significant reduction in the 1-year recurrence rate, from 28% using simple compression to 12% using surgery and compression (P < .0001). In our population of patients with ulcers CEAP C6 evaluated for 52 weeks, after all varicose veins had been treated, considering those completely healed and those who showed a decrease of >50% in the ulcer diameter, the total improvement was 88%.
Chaby et al15 conducted a multicenter cohort study in which they evaluated >50% reduction in wound diameter after 4 weeks of treatment. When comparing ulcers that healed completely with those that did not, they concluded that the reduction in ulcer area was significantly associated with the possibility of complete healing (odds ratio, 1.6; 95% confidence interval [CI], 1.0-2.14). Diameter reduction was considered as an independent factor. These findings were like those found by Kantor and Margolis,16 which corroborates our results.
The EVRA (Early Venous Reflux Ablation)17 randomized study showed faster healing and longer ulcer-free time for the group treated with endovenous ablation of axial reflux in the lower limbs. Ulcer healing time was shorter in the early intervention group and more patients healed completely (HR for healed ulcer, 1.38; 95% CI, 1.13 to 1.68; P = .001). Median healing time was 56 days (95% CI, 49 to 66) in the early treatment group and 82 days (95% CI, 69 to 92) in those with delayed intervention. Healing rate at 24 months was 85.6% in the early treatment group and 76.3% in the group who used compression alone. These patients had ulcers with less than 6 months of evolution and high compliance with compression. Endovenous laser (EVLA), radiofrequency (RFA), ultrasound guided foam sclerotherapy, as well as cyanoacrylate and mechanochemical ablation were performed in combination or alone. All patients in our cohort used foam as the sole method of endovenous ablation associated with elastic or inelastic compression for 24 hours immediately after the procedure and throughout the treatment, evaluating the benefit of correcting axial reflux and compression together. In 52 weeks, 56% of the ulcers had healed and continued monitoring for more than one year showed that 32% of the patients whose ulcers were still partially open achieved healing. In our cohort, the use of compression favored healing in 145 patients compared with those who did not adhere to compression treatment (93.0% vs 7.1%; P < .001).
Although all endovenous ablation techniques can be used to treat varicose veins and correct venous hypertension, speeding up the healing process, foam proved to be effective in our cohort. As it does not require tumescent anesthesia, has a low operating cost, is easy to perform and is widely disseminated5,18 the method stands out as a relevant technique in caring for these CEAP C6 patients with comorbidities who can use only the public health service. Considering each sclerotherapy session using only the materials as a reference, ultrasound-guided foam treatment costs between US$1.30-1.50, compared with approximately US$295.00 spent on laser fiber, for the Brazilian public health system. Although the randomized CLASS (Comparison of Laser, Surgery, and Foam Sclerotherapy)19 trial demonstrated the cost-effectiveness of laser therapy, 31% of these patients underwent subsequent foam treatment, likely contributing to the success, as mentioned by Cartee et al.20 Patients with limited movement of the tibiotarsal joint had a worse healing rate. Of 77 individuals, only three (1.9%; P < .001) healed completely, and probably the use of compression had no benefit in these patients as an additional factor for success, compared with those who did not use it (36.5% vs 63.5% P = .702). Parker at al,2 in a literature review, found that lack of mobility, use of supports for walking (eg, crutches and walkers), reduced mobility of the ankle joint with varying degrees of movement restriction, are associated with significant reduction of ulcer healing rate at 24 and 52 weeks in two studies with 50 to 189 participants (hazard ratio 1.08, 95% CI 1.03-1.13, P = .001). Conversely, Omar Mutlak et al showed that in patients who exercised with mobilization of the tibiotarsal joint, ulcer size decreased significantly (P < 0.001) after 3 months.21 In our study, patients who had reduced dorsiflexion of the ankle healed with greater difficulty, highlighting the importance of mobilizing this joint especially in larger diameter wounds.
Ulcers with more than 6 months of evolution had worse healing; only 24 patients healed (15.4% vs 70.7% P < .001). In a retrospective analysis of 554 patients evaluated over a 3-year period, Yang GK et al22 identified ulcer size and late treatment as factors influencing non-healing or delayed healing. Those with increased wound diameter required a longer time for complete resolution, associated with remodeling of the subcutaneous tissue that can prolong healing and is subject to infection, which contributes to delayed healing. Delayed healing in our population was also associated with treatment onset and the frequency of foam sessions which occurred at intervals greater than thirty days, suggesting that increasing the number of applications could speed up the healing process.
In a retrospective cohort study conducted by the University of Medicine in São Paulo, Brazil, between 2000 and 2010, 94 patients (137 legs) were treated exclusively with compression therapy. The study found a reduction in ulcer area of 50% or more in 40.1% of patients (95% CI: 31.9%-48.4%) at six months and 49.6% (95% CI: 41.2%-58.1%) at 12 months. Complete healing was achieved in 16.8% of patients (95% CI: 10.5%-23.1%) at six months and 27% (95% CI: 19.5%-39.5%) at 12 months. These findings demonstrate that compression therapy alone yields a relatively low healing rate, emphasizing the need to address axial reflux to improve treatment outcomes.23
Our cohort had a satisfactory healing rate, although slightly lower when compared with the literature. This difference may be due to some patient characteristics: all participants are of low socioeconomic status, with difficulties in accessing the public health system and low adherence to wound care measures and compression therapy. The foam application regime, whose periodicity and frequency had a considerable interval, could explain the incidence of recanalization of the treated vein, maintenance of venous hypertension and difficulty in healing. After 52 weeks of observation, 89 more patients (32%) completely healed with repeated foam application, suggesting that a longer follow-up and treatment period would be necessary for certain patients. Foam had benefits even for those who did not heal completely, as they showed a considerable pain reduction, improved wound appearance, less exudate and fewer dressing changes, impacting quality of life.
Conclusions
Impacts on the quality of life of patients with chronic venous ulcers, which are often unmeasured, and the expenses burdening the public health system draw attention to the importance of early and effective management of these individuals. This study demonstrated, consistent with the literature, that the use of foam combined with compression is a cost-effective treatment. It can be considered a first-line option not only for older and frail patients with venous ulcers, who are typically not candidates for surgical interventions, but also for individuals with limited financial resources who rely on the public health system. Age has been shown to be a risk factor that deserves to be considered in patients with severe venous insufficiency. Early intervention in venous disease prevents its progression to a more advanced phase, where treatment results are much less promising. Moreover, we confirmed that the time of evolution and ulcer size are indicators of a worse prognosis. Local changes owing to ulcer presence, such as muscle hypotrophy and osteoarticular changes, have been shown to make healing difficult or even impossible and reinforce the need for a multidisciplinary approach for these patients, which could contribute to the success of treatment with foam.
Author contributions
Conception and design: AB, EN
Analysis and interpretation: AB, EN
Data collection: AB, NB, CH, PB, CA, ER, RA
Writing the article: AB, EN
Critical revision of the article: AB, EN, NB, CH, PB, CA, ER, RA
Final approval of the article: AB, EN, NB, CH, PB, CA, ER, RA
Statistical analysis: EN
Obtained funding: Not applicable
Overall responsibility: AB
Funding
None.
Disclosures
None.
Footnotes
The editors and reviewers of this article have no relevant financial relationships to disclose per the Journal policy that requires reviewers to decline review of any manuscript for which they may have a conflict of interest.
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