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We report the first clinical evaluation of a new enzymatic wound debridement product containing tarumase in venous leg ulcer patients. As a first-in-human study, this was a prospective, open-label, multi-centre, dose escalation study across five dose cohorts and involving a total of 43 patients treated three times weekly for up to 4 weeks (12 applications). The primary and secondary endpoints of the study were to assess the systemic safety, local tolerability, and early proof of concept both for wound debridement and healing. Results indicated that the tarumase enzyme was well tolerated when applied topically to wounds, with no indications of systemic absorption, no evidence of antibody generation, and no systemic effects on coagulation pathways. Locally, there was no evidence of pain on application, no local itching, no increases in erythema, oedema, exudate or bleeding and only a few treatment emergent adverse events were reported. As the concentration of tarumase was escalated, trends towards faster and improved effectiveness of wound debridement were observed, especially in patients with significant slough at baseline. Trends towards faster rates of healing were also noted based on observations of increased granulation tissue, increased linear healing and reduction in surface area over the 4-week treatment period., (© 2024 SolasCure Ltd. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Background: Large studies that examine risk factors for first occurrence of venous leg ulcerations are needed to guide management., Objective: To investigate factors associated with development of first occurrence of venous leg ulcerations., Methods: A retrospective cohort study using a validated national commercial claims database of patients with venous insufficiency. Subjects were followed to determine whether they developed first occurrence of venous leg ulcerations, and risk and protective factors were analyzed., Results: Adjusted hazard ratio (AHR) for comorbidities demonstrated an increased risk in men (AHR 1.838; 95% confidence interval [CI] 1.798-1.880), older age (45-54 years: AHR 1.316, 95% CI 1.276-1.358; 55-64 years, AHR 1.596, 95% CI 1.546-1.648), history of nonvenous leg ulceration (AHR 3.923; 95% CI 3.699-4.161), anticoagulant use (AHR 1.199; 95% CI 1.152-1.249), antihypertensive use (AHR 1.067; 95% CI 1.040-1.093), and preexisting venous insufficiency including chronic venous insufficiency (AHR 1.244; 95% CI 1.193-1.298), edema (AHR 1.224; 95% CI 1.193-1.256), and chronic venous hypertension (AHR 1.671; 95% CI 1.440-1.939). Possible protective factors were having venous surgery (AHR 0.454; 95% CI 0.442-0.467), using compression stockings (AHR 0.728; 95% CI 0.705-0.753), using prescribed statin medications (AHR 0.721; 95% CI 0.700-0.743), and using pain medications (AHR 0.779; 95% CI 0.757-0.777)., Limitations: Risk of misclassification, given the use of International Classification of Diseases, Ninth Revision codes. Possible confounding factors such as body mass index could not be adequately controlled with these codes., Conclusion: The new evidence presented supports a paradigm shift toward venous leg ulceration prevention., (Copyright © 2020. Published by Elsevier Inc.)

Venous leg ulcers (VLU) comprise about 70% of lower leg wounds and cost more than 14 billion USD per year. Patients with VLU are often admitted to the hospital; however, epidemiological study of this important patient subset is challenged by lack of validated database search protocol. Five International Classification of Diseases (ICD) 9 codes were identified for their relationship with VLUs (454.0, 454.2, 459.11, 707.9, and 707.10). The ICD9 code was considered to successfully predict a VLU if the wound was located in the gaiter area and had either relevant clinical findings, a positive venous study, and/or a diagnosis of VLU written in the physician note. The code 454.0, when combined with length of admission and subjects' age, yielded high specificity (100%) and positive predictive value (100%), sacrificing sensitivity (34.4%). This formula represents a viable search criterion to identify VLU patients in large-scale datasets to examine patients' outcomes, costs, and comorbidities., (© 2019 by the Wound Healing Society.)

Objective: This systematic review and meta-analysis aimed to assess whether compression stockings or other interventions reduce the incidence of venous ulceration after acute deep venous thrombosis., Methods: We searched PubMed and Embase for randomized controlled trials (RCTs), restricted to English, Spanish, and Hebrew, related to post-thrombotic syndrome and venous ulceration in participants with confirmed deep venous thrombosis. Our primary statistical assessment was the Peto odds ratio (OR)., Results: Our search generated 23 RCTs meeting inclusion and exclusion criteria, summing 6162 patients and 146 ulcerative events. Trials were categorized into compression, low-molecular-weight heparin (LMWH), procedural thrombolysis, medical thrombolysis, or miscellaneous. Six compression trials were identified, of which five were included in meta-analysis. Compression compared with placebo did not reduce venous ulceration (OR, 0.915; 95% confidence interval [CI], 0.475-1.765), and long-term compression was not superior to short-term compression (OR, 1.36; 95% CI, 0.014-1.31). Four LMWH trials were identified but were not subjected to meta-analysis because of intertrial heterogeneity. One trial, comparing extended tinzaparin with warfarin, demonstrated eight ulcers in the warfarin group and one ulcer in the LMWH group (relative risk, 0.125; P < .05). Three procedural thrombolysis trials were pooled into meta-analysis; fewer ulcerative events occurred in procedural thrombolysis patients, but the effect was not significant (OR, 0.677; 95% CI, 0.338-1.358). Eight medical thrombolysis trials were identified. Pooled analysis of five trials demonstrated a protective effect on ulceration in streptokinase patients vs standard heparinization (OR, 0.125; 95% CI, 0.021-0.739). However, these trials were of poor-quality study design, had small sample size, and had poor overall outcomes. Miscellaneous studies included a trial of hidrosmina, a vasoactive flavonoid, and a trial comparing 6-month warfarin treatment with 6 weeks; neither trial had significant outcomes. Intertrial heterogeneity was not adequately assessed with the I 2 value as venous ulceration is a rare event; the Grading of Recommendations Assessment, Development, and Evaluation evidence for most trials was very low, with the exception of procedural thrombolysis trials, for which it was low., Conclusions: We found insufficient evidence to assess whether compression or other interventions protect against venous ulceration. To develop guidelines for treatment decisions related to prevention of venous ulceration, high-powered RCTs investigating venous leg ulcers as a primary outcome are required., (Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Introduction: Chronic venous insufficiency (CVI) affects up to one-third of the adult population yet venous leg ulcers (VLU), a significant complication of CVI, only affect 1%-2% of adults in the USA. Why some develop VLU and others do not is unclear. VLU have a significant impact on quality of life and are extremely costly and difficult to treat. Moreover, VLU prevalence is increasing, doubling in the last 20 years. In order to characterise the differences between people with CVI and those who ultimately develop VLU, we aim to set up the unique venous insufficiency in South Florida cohort., Methods and Analysis: Subjects will be recruited from the University of Miami Hospital and Clinic's vascular laboratory database, which began in July 2011. Any adult age 18-95 who has had venous reflux detected on duplex ultrasound of the lower extremities is included. Approximately 2500 patients are already in the database that meet these criteria, with an estimated 2500 additional potential subjects to be recruited from the vascular laboratory database over the next 5 years. Subjects with a history of VLU prior to the duplex study date will be excluded. Data will be collected via review of the Doppler study report, patient phone interview and review of the electronic medical record. Subjects will be contacted for follow-up every 3 months for at least 5 years until the study endpoint, development of first VLU (fVLU), is reached. In order to estimate the time from reflux documentation to fVLU, Kaplan-Meier survival curves will be constructed. Cox proportional hazard regression models will be constructed to investigate possible risk factors., Ethics and Dissemination: This study is approved by the University of Miami's Institutional Review Board. We hope to present the results of this study to the scientific community at conferences and in peer-reviewed journals., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

This issue provides a clinical overview of venous leg ulcers, focusing on prevention, diagnosis, treatment, and practice improvement. The content of In the Clinic is drawn from the clinical information and education resources of the American College of Physicians (ACP), including MKSAP (Medical Knowledge and Self-Assessment Program). Annals of Internal Medicine editors develop In the Clinic in collaboration with the ACP's Medical Education and Publishing divisions and with the assistance of additional science writers and physician writers.