Oral aspirin for treating venous leg ulcers

Background Venous leg ulcers (VLUs) or varicose ulcers are the final stage of chronic venous insufficiency (CVI), and are the most common type of leg ulcer. The development of VLUs on ankles and lower legs can occur spontaneously or after minor trauma. The ulcers are often painful and exudative, healing is often protracted and recurrence is common. This cycle of healing and recurrence has a considerable impact on the health and quality of life of individuals, and healthcare and socioeconomic costs. VLUs are a common and costly problem worldwideprevalence is estimated to be between 1.65% to 1.74% in the western world and is more common in adults aged 65 years and older. The main treatment for a VLU is a firm compression bandage. Compression assists by reducing venous hypertension, enhancing venous return and reducing peripheral oedema. However, studies show that it only has moderate effects on healing, with up to 50% of VLUs unhealed after two years of compression. Non-adherence may be the principal cause of these poor results, but presence of inflammation in people with CVI may be another factor, so a treatment that suppresses inflammation (healing ulcers more quickly) and reduces the frequency of ulcer recurrence (thereby prolonging time between recurrent episodes) would be an invaluable intervention to complement compression treatments. Oral aspirin may have a significant impact on VLU clinical practice worldwide. Evidence for the effectiveness of aspirin on ulcer healing and recurrence in high quality RCTs is currently lacking. Objectives To assess the benefits and harms of oral aspirin on the healing and recurrence of venous leg ulcers. Search methods In May 2015 we searched: The Cochrane Wounds Specialised RegisterThe Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library)Ovid MEDLINEOvid MEDLINE (In-Process & Other Non-Indexed Citations)Ovid EMBASE and EBSCO CINAHL. Additional searches were made in trial registers and reference lists of relevant publications for published or ongoing trials. There were no language or publication date restrictions. Selection criteria We included randomised controlled trials (RCTs) that compared oral aspirin with placebo or no drug intervention (in the presence or absence of compression therapy) for treating people with venous leg ulcers. Our main outcomes were time to complete ulcer healing, rate of change in the area of the ulcer, proportion of ulcers healed in the trial period, major bleeding, pain, mortality, adverse events and ulcer recurrence (time for recurrence and proportion of recurrence). Data collection and analysis Two review authors independently selected studies for inclusion, extracted data, assessed the risk of bias of each included trial and assessed overall quality of evidence for the main outcomes in the 'Summary of findings' table. Main results The electronic search located 62 studies. We included two RCTs of oral aspirin (300 mg/daily) given in addition to compression compared with compression and placebo, or compression alone. To date, the impact of aspirin on VLUs has been examined by only two randomised clinical trials, both with a small number of participants. The first RCT was conducted in the United Kingdom (n=20) and reported that daily administration of aspirin (300mg) in addition to compression bandages increased both the rate of healing, and the number of participants healed when compared to placebo in addition to compression bandaging over a four month period. Thirty-eight per cent of the participants given aspirin reported complete healing compared with 0% in the placebo group. Improvement (assessed by reduction in wound size) occurred in 52% of the participants taking aspirin compared with 26% in those taking placebo). The study identified potential benefits of taking aspirin as an adjunct to compression but the sample size was small, and neither the mechanism by which aspirin improved healing nor its effects on recurrence were investigated. In 2012 an RCT in Spain (n=51) compared daily administration of aspirin (300mg) in addition to compression bandages with compression alone over a five month period. There was little difference in complete healing rates between groups (21/28 aspirin and 17/23 compression bandages alone) but the average time to healing was shorter (12 weeks in the treated group vs 22 weeks in the compression only group) and the average time for recurrence was longer in the aspirin group (39 days: [SD 6.0] compared with 16.3 days [SD 7.5] in the compression only group). Although this trial provides some limited data about the potential use of aspirin therapy, the sample size (only 20 patients) was too small for us to draw meaningful conclusions. In addition, patients were only followed up for 4 months and no information on placebo was reported. Authors' conclusions Low quality evidence from two trials indicate that there is currently insufficient evidence for us to draw definitive conclusions about the benefits and harms of oral aspirin on the healing and recurrence of venous leg ulcers. We downgraded the evidence to low quality due to potential selection bias and imprecision due to the small sample size. The small number of participants may have a hidden real benefit, or an increase in harm. Due to the lack of reliable evidence, we are unable to draw conclusions about the benefits and harms of oral daily aspirin as an adjunct to compression in VLU healing or recurrence. Further high quality studies are needed in this area.Evidence Based Actions Department From Marilia Medical School - FAMEMA, BrazilFAPESP-Fundacao de Amparo a Pesquisa do Estado de Sao Paulo, BrazilNational Institute for Health ResearchEvidence Based Health Actions Department and Thoracic Surgery Department, Marilia Medical School, Marilia, BrazilDepartment of Medicine, Federal University of São Paulo, São Paulo, BrazilDepartment of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, AustraliaDepartment of Medicine, Federal University of São Paulo, São Paulo, BrazilWeb of Scienc

Protocol for a pilot randomised controlled clinical trial to compare the effectiveness of a graduated three layer straight tubular bandaging system when compared to a standard short stretch compression bandaging system in the management of people with venous ulceration: 3VSS2008

<p>Abstract</p> <p>Background</p> <p>The incidence of venous ulceration is rising with the increasing age of the general population. Venous ulceration represents the most prevalent form of difficult to heal wounds and these problematic wounds require a significant amount of health care resources for treatment. Based on current knowledge multi-layer high compression system is described as the gold standard for treating venous ulcers. However, to date, despite our advances in venous ulcer therapy, no convincing low cost compression therapy studies have been conducted and there are no clear differences in the effectiveness of different types of high compression.</p> <p>Methods/Design</p> <p>The trial is designed as a pilot multicentre open label parallel group randomised trial. Male and female participants aged greater than 18 years with a venous ulcer confirmed by clinical assessment will be randomised to either the intervention compression bandage which consists of graduated lengths of 3 layers of elastic tubular compression bandage or to the short stretch inelastic compression bandage (control). The primary objective is to assess the percentage wound reduction from baseline compared to week 12 following randomisation. Randomisation will be allocated via a web based central independent randomisation service (nQuery v7) and stratified by study centre and wound size ≤ 10 cm²or >10 cm². Neither participants nor study staff will be blinded to treatment. Outcome assessments will be undertaken by an assessor who is blinded to the randomisation process.</p> <p>Discussion</p> <p>The aim of this study is to evaluate the efficacy and safety of two compression bandages; graduated three layer straight tubular bandaging (3L) when compared to standard short stretch (SS) compression bandaging in healing venous ulcers in patients with chronic venous ulceration. The trial investigates the differences in clinical outcomes of two currently accepted ways of treating people with venous ulcers. This study will help answer the question whether the 3L compression system or the SS compression system is associated with better outcomes.</p> <p>Trial Registration</p> <p>ACTRN12608000599370</p

A clinically compatible drug-screening platform based on organotypic cultures identifies vulnerabilities to prevent and treat brain metastasis

We report a medium‐throughput drug‐screening platform (METPlatform) based on organotypic cultures that allows to evaluate inhibitors against metastases growing in situ. By applying this approach to the unmet clinical need of brain metastasis, we identified several vulnerabilities. Among them, a blood–brain barrier permeable HSP90 inhibitor showed high potency against mouse and human brain metastases at clinically relevant stages of the disease, including a novel model of local relapse after neurosurgery. Furthermore, in situ proteomic analysis applied to metastases treated with the chaperone inhibitor uncovered a novel molecular program in brain metastasis, which includes biomarkers of poor prognosis and actionable mechanisms of resistance. Our work validates METPlatform as a potent resource for metastasis research integrating drug‐screening and unbiased omic approaches that is compatible with human samples. Thus, this clinically relevant strategy is aimed to personalize the management of metastatic disease in the brain and elsewhere

BacHBerry: BACterial Hosts for production of Bioactive phenolics from bERRY fruits

BACterial Hosts for production of Bioactive phenolics from bERRY fruits (BacHBerry) was a 3-year project funded by the Seventh Framework Programme (FP7) of the European Union that ran between November 2013 and October 2016. The overall aim of the project was to establish a sustainable and economically-feasible strategy for the production of novel high-value phenolic compounds isolated from berry fruits using bacterial platforms. The project aimed at covering all stages of the discovery and pre-commercialization process, including berry collection, screening and characterization of their bioactive components, identification and functional characterization of the corresponding biosynthetic pathways, and construction of Gram-positive bacterial cell factories producing phenolic compounds. Further activities included optimization of polyphenol extraction methods from bacterial cultures, scale-up of production by fermentation up to pilot scale, as well as societal and economic analyses of the processes. This review article summarizes some of the key findings obtained throughout the duration of the project

Evidence summary:pressure injury identification benchmarking

Pressure injuries (PIs) are a significant health issue worldwide, and contribute substantially towards the economic burden in healthcare systems. This is primarily because PIs increase the length of hospital stays; and longer hospital stays also predict PI development. PIs are also used to measure the performance of health staff and facilities in a variety of settings. Inappropriate management of PIs can lead to further complications, necessitating an increase in resources in the hospital for assessment, monitoring and treatment. However, over time, challenges in regard to identifying, assessing and reporting PIs have proven to be problematic for a number of reasons. This paper explains the main challenges to PI assessment, and presents a series of best practice recommendations to rectify these challenges.</jats:p

Ankle Brachial Pressure Index and compression application:review summary

Venous leg ulcers (VLUs) are a significant complication amongst persons with chronic venous insufficiency (CVI) that frequently follow a cycle of healing and recurrence. Current clinical practice guidelines (CPGs) recommend applying below knee compression to improve VLU healing. Compression could be applied if the Ankle Brachial Pressure Index (ABPI) rules out significant arterial disease, as sufficient peripheral arterial circulation is necessary to ensure safe compression use. We conducted a content analysis of 13 global CPGs on the accuracy of recommendations related to ABPI and compression application. Eight CPGs indicated that compression is recommended when the ABPI is between 0.8 and 1.2 mmHg. However, this review found there is disagreement between 13 global VLU CPGs, with a lack of clarity on whether or not compression is indicated for patients with ABPIs between 0.6 and 0.8 mmHg. Some CPGs recommend reduced compression for treatment of VLUs, while others do not recommend any type of compression at all. This has implications for when it is safe to apply compression, and the inconsistency in evidence indicates that specialist advice may be required at levels beyond the ABPI &ldquo;safe&rdquo; range listed above.</jats:p