An estimate of the economic burden of venous leg ulcers associated with deep venous disease.

INTRODUCTION: Venous leg ulcers (VLU) embody the most severe stage of the broad spectrum of chronic venous disease. Approximately 40% of patients with VLU present with the underlying deep venous disease (DVD). Although the data are scarce, these deep venous disease-related VLU (DRV) are thought to have higher recurrence rates and a substantial economic burden. The objective of this study was to assess the economic burden of DRV across Australia, France, Germany, Italy, Spain, the UK, and the USA. METHODS: A comprehensive literature review was undertaken to identify publications documenting the incidence and prevalence of VLU and DRV, medical resource utilization, and associated costs of DRV. Findings from this literature review were used to estimate the economic burden of illness, including direct medical costs over a 12-month interval following initial presentation of a newly formed DRV. RESULTS: Total annual incidence of new or recurrent DRV in Australia, France, Germany, Italy, Spain, UK, and the US are estimated at 122,000, 263,000, 345,000, 253,000, 85,000, 230,000, and 643,000 events, respectively, in 2019. Incidence ranges from 0.73 to 3.12 per 1000 persons per year. The estimated annual direct medical costs for patients managed conservatively in these geographies total ~ $10.73 billion (USD) or $5527 per person per year. CONCLUSION: The availability of published data on the costs of VLU care varies widely across countries considered in this analysis. Although country-specific VLU practice patterns vary, there is a uniform pattern of high-cost care.

Systematic review and meta-analysis of deep venous reflux correction in chronic venous insufficiency.

OBJECTIVE: The aim of this study was to investigate the technical feasibility, operative techniques, safety, and efficacy outcomes of procedures aimed at correcting deep venous reflux, in patients with chronic venous insufficiency. METHODS: We performed systematic literature searches in PubMed, Embase, and Web of Science from databases' inception to February 2022. We included systematic reviews, randomized controlled trials, and observational studies describing surgical procedures to treat patients with deep reflux due to primary and secondary incompetence, post-thrombotic syndrome (PTS). Proportion meta-analyses were performed for all the efficacy and safety outcomes. RESULTS: We included 57 studies in the quantitative synthesis: three randomized controlled trials including 252 patients and 54 case series including 4004 patients. Studies included a median of 38 patients, with a mean age of 51 years; 52% of them were males. Forty percent of studies included 2291 patients with primary incompetence, 29% of studies included 595 patients with PTS, and 31% of studies included 1118 patients with both diseases. As for primary incompetence, pooled estimates for all procedures showed an 89% (95% confidence interval [CI], 82%-94%) of ulcer healing, 10% (95% CI, 4%-18%) ulcer recurrence, 98% (95% CI, 93%-100%) valve patency, 84% (95% CI, 78%-90%) valve competence, 0.05% (1/1904 patients) pulmonary embolism, 1% (95% CI, 0%-3%) wound infections, 5% (95% CI, 1%-9%) hematoma, 2% (95% CI, 0%-6%) lymphocele, 2% (95% CI, 1%-4%) thrombosis, 85% (95% CI, 74%-94%) pain improvement, 89% (95% CI, 65%-100%) edema improvement, and 85% (95% CI, 73%-93%) lipodermatosclerosis improvement. Patients with PTS showed less favorable outcomes: 82% (95% CI, 71%-91%) of ulcer healing, 18% (95% CI, 5%-36%) ulcer recurrence, 88% (95% CI, 78%-96%) valve patency, 78% (95% CI, 66%-88%) valve competence, no pulmonary embolism, 6% (95% CI, 0%-22%) wound infections, 6% (95% CI, 3%-10%) hematoma, 5% (95% CI, 1%-12%) lymphocele, 7% (95% CI, 1%-16%) thrombosis, 79% (95% CI, 59%-94%) pain improvement, 75% (95% CI, 61%-88%) edema improvement, and 64% (95% CI, 9%-100%) lipodermatosclerosis improvement. CONCLUSIONS: The number of studies included in each meta-analysis are limited, and knowing how this element can affect the statistical power, as well as the absence of comparative control groups, it is not possible to draw definitive conclusions. Nevertheless, deep venous reconstructive surgery for reflux may increase the probability of clinical improvement in patients affected by chronic venous insufficiency. Outcomes appear to be satisfactory even if possible adjunctive procedures may be required over the course of the patient's lifetime. Consequently, a strict follow-up protocol is required to maintain outcomes. Further studies are required to evaluate deep venous reconstructive surgery for reflux particularly as to how it compares with the more recently introduced endovenous approaches.

Time-Driven Activity-Based Costing for Capturing the Complexity of Healthcare Processes: The Case of Deep Vein Thrombosis and Leg Ulcers.

Time-driven activity-based costing (TDABC) is suggested to assess costs within the value-based healthcare approach, but there is a paucity of applications in chronic diseases such as deep vein thrombosis (DVT) and leg ulcers. In this context, we applied TDABC in a cost-effectiveness analysis comparing venous stenting to compression ± anticoagulation (standard of care-SOC) from both hospital and societal perspectives in Italy. TDABC was applied to both treatments to assess costs that were included in a cost-effectiveness model. Clinical inputs were retrieved from the literature and integrated with real-world data. The Incremental Cost Utility Ratio (ICUR) of stenting compared to SOC was EUR 10,270/QALY and EUR 8962/QALY for hospital and societal perspectives, respectively. The mean cost per patient for venous stenting of EUR 5082 was higher than the Diagnosis-Related Group (DRG) reimbursement (EUR 4742). For SOC, an ulcer healing in 3 months costs EUR 1892, of which EUR 302 (16%) is borne by the patient versus a reimbursement of EUR 1132. TDABC showed that venous stenting may be cost-effective compared with SOC but that reimbursement rates may not completely cover the real costs, which are partially sustained by the patients. A more efficient policy for covering the real costs may be beneficial for both clinical centers and patients.

Residual volume fraction during walking using wireless air plethysmography in patients with chronic deep venous disease.

OBJECTIVE: Traditional air plethysmography (APG) provides a quantitative measure of the residual volume fraction (RVF) after 10 tiptoe movements. The recent development of a wireless Bluetooth (Bluetooth SIG, Inc, Kirkland, Wash) APG device, the PicoFlow (Microlab Elettronica, Padua, Italy), enabled us to measure RVF during normal walking. The aim of our study was to compare the RVF obtained during tiptoeing with RVF obtained during normal walking in patients with deep venous pathology (ie, reflux and/or obstruction). METHODS: A total of 61 consecutive symptomatic patients (27 women and 34 men; median age, 46 years; range, 18-79 years) with chronic venous disease due to deep venous pathology (venous reflux or obstruction, or both) before treatment or persisting after intervention were included in the present study. Of the 122 total limbs examined, 79 were affected by deep chronic venous disease and 43 contralateral limbs were normal with normal deep veins and acted as controls. The APG examination was performed using the PicoFlow device using the standard examination technique. The RVF was calculated from the residual volume at the end of 10 tiptoe movements and also during normal walking. RESULTS: At the end of the 10 tiptoe movements, the mean ± standard deviation RVF was 27.0% ± 13.2% in the limbs with normal deep veins and 38.8% ± 16.9% in the limbs with deep chronic venous disease (P < .001). During walking, when a steady state in volume was reached, the RVF was 26.3% ± 17.8% in the limbs with normal deep veins and 43.1% ± 18.6% in limbs with deep venous disease (P < 0.001). A significant difference was found between limbs with normal deep veins and limbs with deep venous reflux, irrespective of which exercise was performed. However, the mean RVF between the limbs with normal deep veins and those with outflow obstruction in the absence of reflux was significant during walking (P = .012) but not during tiptoeing (P = .212). The mean RVF was higher in the C3 to C6 limbs than in the C0 to C2 limbs with tiptoeing (29.9% ± 14.5% vs 38.3% ± 17.0%; P < .006). Similar results were obtained with walking (29.2% ± 18.0% vs 42.4% ± 18.8%; P < .004). CONCLUSIONS: In limbs with normal deep veins and deep veins with reflux, the RVF measured during walking with wireless APG was similar to the RVF obtained during tiptoeing. However, in the limbs with outflow obstruction in the absence of reflux, the RVF during walking was higher than the RVF after tiptoeing. Our results have shown that the evaluation of RVF during walking is feasible and practical.

Clinical guidelines versus current clinical practice for the management of deep vein thrombosis.

BACKGROUND: Deep vein thrombosis (DVT) is one of the major health problems worldwide with potentially serious outcomes related to mortality and morbidity. We provide a current view on how patients with DVT are managed in routine practice compared with the recommendations of published clinical guidelines. METHODS: A literature review was conducted on studies reporting diagnostic and treatment patterns for acute DVT. Four dimensions were evaluated to compare the differences between clinical practice and clinical guidelines recommendations: diagnostic pathway, prescription of pharmacologic treatment and related duration, and prescription of compression therapy. For each aspect, the agreement with the corresponding guideline has been estimated as a percentage ranging from 0% (no agreement) to 100% (full agreement). RESULTS: Sixteen studies reported clinical practices in 10 countries. Among them, Japan showed the highest agreement with guidelines, followed by the UK and Switzerland. Hong Kong showed the highest agreement with diagnosis guidelines, Spain for drug treatment, UK for treatment duration, and France for compression therapy. Conversely, Germany reported a complete disagreement with guidelines for diagnosis, followed by low agreement level by UK and Italy, and Switzerland reported a lower agreement level with prescription of compression therapy. CONCLUSIONS: The implementation of clinical guidelines for the management of patients with DVT varies among countries from strict adherence to a complete lack of adherence. In this context, registries may be a useful tool to analyze clinical practice and produce findings that may be generalizable across populations.

Venous stenting for patients with outflow obstruction and leg ulcers: cost-effectiveness and budget impact analyses.

Aim: To perform cost-effectiveness analysis (CEA) and budget impact analysis (BIA) comparing stenting to standard medical treatment (SMT) for the management of deep venous outflow obstruction and leg ulcers from the Italian Healthcare Service perspective. Materials & methods: A Markov model was developed to project costs and quality-adjusted life-years (QALYs) over 3 years, based on data from literature combined with real-world data. Moreover, a BIA was performed comparing the current scenario (100% SMT) with increasing utilization rates of stenting over SMT from 0.5 to 5%, in the next 5 years. Results: Stenting is a cost-effective (incremental cost-utility ratio €12,388/QALY) or dominant option versus SMT, according to in-patient or day-hospital settings, respectively. Increasing use of stenting over SMT, in the next 5 years, is expected to yield additional costs of 39.5 million Euros (in-patient) or savings of 5.1 million Euros (day-hospital). Conclusion: Stenting is a cost-effective option compared with SMT for patients with deep vein occlusion and ulceration in Italy.

Neovalve construction in deep venous incompetence.

OBJECTIVES: The purpose of this study is to assess the outcome of neovalve construction in two consecutive series of patients affected by postthrombotic syndrome and valve agenesis. The technique was modified in the second series so as to correct a cause of failure. METHODS: Between December 2000 and June 2007, 40 neovalve constructions were carried out in 36 patients (19 males, 17 females, median age 57, range, 29-82) affected by deep venous insufficiency. Thirty-two patients were affected by postthrombotic syndrome and 4 by valve agenesis. The 32 patients with postthrombotic syndrome were selected from among 76 patients with resistant ulcers classified C (6,S) E (S) A (S,D,P) P (R,RO) and the 4 patients with valve agenesis were selected from among 28 affected by resistant ulcers classified as C (6,S) E (C) A (S,D,P) P (R). The patients were subdivided into 2 groups. The first group included 19 operations performed in the period between December 2000 and December 2004, with a median follow-up of 54 months (range, 31-78). The second group included 21 patients operated on between January 2005 and June 2007, with a median follow-up of 5 months (range, 2-29). In the second group, a surgical variation was applied in order to prevent flap collapse and to maintain the continence of the neovalve. RESULTS: In the first series, ulcer healing was observed in 16 cases out of 19 (84%). Recurrent ulcers were observed in one case after 3 years. Valve competence was ascertained in 13 cases per 803 patient-months (1.6/100 patient-months). With regard to the second series, competence was achieved in all cases with a cumulative rate of 21 per 228 patient-months (9.2/100 patient-months). In the second series, the ulcer failed to heal in one case and recurred in two cases, with an intention-to-treat ulcer recurrence rate of three cases per 209 patient-months. Postoperative deep-venous thrombosis was observed in 3 patients in the first series. None was detected in the second series. The mortality rate was 0 and in neither group was pulmonary embolism detected. CONCLUSION: The modified technique applied to the second group seemed to improve valve continence results significantly. However, a longer follow-up period is required for the latter group to validate this technical enhancement.

Investigation of non-saphenous veins in C0S patients.

BACKGROUND: C0S patients have symptoms of chronic venous disorders (CVDs), though an anatomical or pathophysiological explanation is lacking. C0 and C1 classified lower limbs can present with valve incompetence from the second to sixth generation of tributaries of saphenous veins despite the absence of a detectable saphenous truncal reflux. We hypothesized that C0S venous symptoms could stem from the second to sixth generation of saphenous tributaries and small veins that are not connected to the saphenous system. The aim was to explore these veins in C0S subjects and compare them with asymptomatic C0A subjects. METHODS: This was an open, controlled study enrolling 36 subjects, where C0S patients (N.=18) were compared with asymptomatic C0A subjects (N.=18). The VAS (visual analog scale) was used to assess leg pain. Veins were assessed using B-flow ultrasound (valve anatomy), continuous-wave (CW) Doppler (flow patterns), biomicroscopy (visualization of nutritional vessels), laser Doppler flowmetry (quantify supine microvascular perfusion) and quantitative digital photo-plethysmography (PPG) (measuring post-exercise venous refilling time [VRT]). RESULTS: There were no significant differences between C0S and C0A subjects in terms of microvascular perfusion (laser-Doppler), nutritional vessels (biomicroscopy) and VRT (PPG). B-flow ultrasound was unable to acquire sufficient data in second generation saphenous tributaries. However, the CW Doppler identified two different flow patterns: uni- and bidirectional. Bidirectional flow was significantly (P=0.05) higher in C0S versus C0A patients. CONCLUSIONS: CW Doppler, using a flat high-sensitivity probe, revealed the presence of a bidirectional flow that was significantly (P=0.05) higher in C0S than in control patients, suggesting the presence of reflux in non axial veins. These data give a new perspective on the management of C0S patients.

Venous hemodynamic changes in lower limb venous disease: the UIP consensus according to scientific evidence.

There are excellent guidelines for clinicians to manage venous diseases but few reviews to assess their hemodynamic background. Hemodynamic concepts that evolved in the past have largely remained unchallenged in recent decades, perhaps due to their often complicated nature and in part due to emergence of new diagnostic techniques. Duplex ultrasound scanning and other imaging techniques which evolved in the latter part of the 20th century have dominated investigation. They have greatly improved our understanding of the anatomical patterns of venous reflux and obstruction. However, they do not provide the physiological basis for understanding the hemodynamics of flow, pressure, compliance and resistance. Hemodynamic investigations appear to provide a better correlation with post-treatment clinical outcome and quality of life than ultrasound findings. There is a far better prospect for understanding the complete picture of the patient's disability and response to management by combining ultrasound with hemodynamic studies. Accordingly, at the instigation of Dr Angelo Scuderi, the Union Internationale de Phlebologie (UIP) executive board commissioned a large number of experts to assess all aspects of management for venous disease by evidence-based principles. These included experts from various member societies including the European Venous Forum (EVF), American Venous Forum (AVF), American College of Phlebology (ACP) and Cardiovascular Disease Educational and Research Trust (CDERT). Their aim was to confirm or dispel long-held hemodynamic principles and to provide a comprehensive review of venous hemodynamic concepts underlying the pathophysiology of lower limb venous disorders, their usefulness for investigating patients and the relevant hemodynamic changes associated with various forms of treatment. Chapter 1 is devoted to basic hemodynamic concepts and normal venous physiology. Chapter 2 presents the mechanism and magnitude of hemodynamic changes in acute deep vein thrombosis indicating their pathophysiological and clinical significance. Chapter 3 describes the hemodynamic changes that occur in different classes of chronic venous disease and their relation to the anatomic extent of disease in the macrocirculation and microcirculation. The next four chapters (Chapters 4-7) describe the hemodynamic changes resulting from treatmen by compression using different materials, intermittent compression devices, pharmacological agents and finally surgical or endovenous ablation. Chapter 8 discusses the unique hemodynamic features associated with alternative treatment techniques used by the CHIVA and ASVAL. Chapter 9 describes the hemodynamic effects following treatment to relieve pelvic reflux and obstruction. Finally, Chapter 10 demonstrates that contrary to general belief there is a moderate to good correlation between certain hemodynamic measurements and clinical severity of chronic venous disease. The authors believe that this document will be a timely asset to both clinicians and researchers alike. It is directed towards surgeons and physicians who are anxious to incorporate the conclusions of research into their daily practice. It is also directed to postgraduate trainees, vascular technologists and bioengineers, particularly to help them understand the hemodynamic background to pathophysiology, investigations and treatment of patients with venous disorders. Hopefully it will be a platform for those who would like to embark on new research in the field of venous disease.

Deep venous reconstructive surgery.

Surgical correction of deep venous reflux is a valuable adjunct in treatment of selected patient with lower limb venous ulcer. Deep venous obstruction and superficial reflux is must be corrected first. Sustained venous ulcer healing and reduced ambulatory venous hypertension can be achieved in patients with both primary and secondary deep venous insufficiency. When direct valve repair is possible, valvuloplasty is the best option, but when this is not feasible, other techniques can be used, including femoral vein transposition into the great saphenous vein, vein valve transplant, neovalve construction, or nonautologous artificial venous valve.

Neovalve construction in postthrombotic syndrome.

OBJECTIVE: The purpose of this study was to evaluate a new neovalve construction technique in postthrombotic syndrome. The surgical procedure is described, and preliminary results of the first case series are given. METHODS: From December 2000 to June 2004, neovalve construction in 18 limbs was performed on 16 patients (8 male and 8 female; median age, 55.5 years; range, 34-79 years) to treat severe chronic venous insufficiency in cases of postthrombotic syndrome. Surgical treatment was recommended in cases of nonhealing or recurrent ulcers (CEAP classification class C6). Preoperative duplex scanning, ascending/descending venography, and air plethysmography were routinely performed. Valvular cusps were created by dissecting the thickened venous wall to obtain material with which to fashion a new monocuspid or bicuspid valve. Mean follow-up was 22 months (range, 1-42 months). Postoperative duplex scanning and air plethysmography were performed in all patients. Descending venography was performed after surgery in 15 limbs. RESULTS: In 16 lower extremities (89%), the ulcer healed within 4 to 25 weeks (median, 12 weeks), and no recurrences occurred. Neovalve competence was confirmed in 17 cases (95%). Postoperative duplex scan and air plethysmography showed a significant improvement in hemodynamic parameters (P < .001), especially in younger patients with good muscle pump function. In 17 limbs (95%), the treated segments remained primarily patent at median follow-up of 22 months. Early thrombosis below the neovalve site occurred in two patients (12%). No perioperative pulmonary embolism was observed. A late occlusion occurred in one patient (6%), 8 months after surgery. Minor postoperative complications occurred in three patients (17%). CONCLUSIONS: Neovalve construction seems to be effective in restoring femoral competence in postthrombotic reflux. Although these preliminary results are encouraging, long-term follow-up and a larger series are required to validate the technique.