•Elevated levels of circulating proinflammatory cytokines are characteristic of inflammaging; age-related systemic inflammation involved in the etiology of many chronic diseases.•This randomized, ...controlled study determined changes in blood plasma levels of proinflammatory cytokines IL-6, IL-1β, and TNF-α in adults in middle to late adulthood before and after dietary supplementation with EPA+DHA (2.5 g/d) or placebo for 8 weeks.•EPA+DHA therapy had a significant lowering effect on levels of IL-6, IL-1β, and TNF-α after 4 weeks and an even greater lowering effect after 8 weeks.•Further, levels of IL-6, IL-1β, and TNF-α were significantly lower in the EPA+DHA Group than the control group at the 4- and 8-week time points.•EPA+DHA therapy may be an effective low-risk dietary intervention for assuaging the harmful effects of inflammaging.
High levels of circulating proinflammatory cytokines are characteristic of inflammaging, a term coined to describe age-related chronic systemic inflammation involved in the etiology of many age-related disorders including nonhealing wounds. Some studies have shown that supplementing diets with n-3 polyunsaturated fatty acids (eicosapentaenoic acid EPA and docosahexaenoic acid DHA) lowers systemic levels of key proinflammatory cytokines associated with inflammaging. However, findings from the few studies that have focused exclusively on older adults are inconclusive. As such, the objective of this randomized controlled study was to test the effects of EPA+DHA therapy on circulating levels of proinflammatory cytokines in adults in middle to late adulthood.
Plasma levels of fatty acids and interleukin (IL)-6, IL-1β and tumor necrosis factor-α (TNF-α) were measured in 35 participants with chronic venous leg ulcers (mean age: 60.6 years) randomnly assigned to 8 weeks of EPA+DHA therapy (2.5 g/d) or placebo therapy.
EPA+DHA therapy had a significant lowering effect on levels of IL-6, IL-1β and TNF-α after 4 weeks of therapy and an even greater lowering effect after 8 weeks of therapy. Further, after adjusting for baseline difference, the treatment group had significantly lower levels of IL-6 (p = 0.008), IL-1β (p < 0.001), and TNF-α (p < 0.001) at Week 4 and at Week 8 IL-6 (p = 0.007), IL-1β (p < 0.001), and TNF-α (p < 0.001) compared to the control group.
Adults in middle to late adulthood receiving EPA+DHA therapy demonstrated significantly greater reductions in circulating levels of proinflammatory cytokines compared with those receiving placebo therapy. EPA+DHA therapy may be an effective low-risk dietary intervention for assuaging the harmful effects of inflammaging.
Sulodexide in venous disease Carroll, B. J.; Piazza, G.; Goldhaber, S. Z.
Journal of thrombosis and haemostasis,
January 2019, 2019-01-00, 20190101, Volume:
17, Issue:
1
Journal Article
Peer reviewed
Open access
Summary
Sulodexide is a glycosaminoglycan extracted from porcine intestinal mucosa. The purpose of this review is to discuss sulodexide's complex pharmacological profile and its clinical applications ...for venous disease. Sulodexide has wide‐ranging biological effects on the vascular system, including antithrombotic, profibrinolytic, anti‐inflammatory, endothelial protective and vasoregulatory effects. Sulodexide has emerged as a potential therapeutic option for the management of chronic venous insufficiency, including venous ulceration, and the prevention of recurrent venous thromboembolism, with a low rate of major bleeding complications. Sulodexide's pleiotropic vascular effects may facilitate the management of common venous disorders.
Chronic wounds impact the quality of life (QoL) of nearly 2.5% of the total population in the United States and the management of wounds has a significant economic impact on health care. Given the ...aging population, the continued threat of diabetes and obesity worldwide, and the persistent problem of infection, it is expected that chronic wounds will continue to be a substantial clinical, social, and economic challenge. In 2020, the coronavirus disease (COVID) pandemic dramatically disrupted health care worldwide, including wound care. A chronic nonhealing wound (CNHW) is typically correlated with comorbidities such as diabetes, vascular deficits, hypertension, and chronic kidney disease. These risk factors make persons with CNHW at high risk for severe, sometimes lethal outcomes if infected with severe acute respiratory syndrome coronavirus 2 (pathogen causing COVID-19). The COVID-19 pandemic has impacted several aspects of the wound care continuum, including compliance with wound care visits, prompting alternative approaches (use of telemedicine and creation of videos to help with wound dressing changes among others), and encouraging a do-it-yourself wound dressing protocol and use of homemade remedies/substitutions.
There is a developing interest in understanding how the social determinants of health impact the QoL and outcomes of wound care patients. Furthermore, addressing wound care in the light of the COVID-19 pandemic has highlighted the importance of telemedicine options in the continuum of care.
The economic, clinical, and social impact of wounds continues to rise and requires appropriate investment and a structured approach to wound care, education, and related research.
Introduction
The adequate use of compression in venous leg ulcer treatment is equally important to patients as well as clinicians. Currently, there is a lack of clarity on contraindications, risk ...factors, adverse events and complications, when applying compression therapy for venous leg ulcer patients.
Methods
The project aimed to optimize prevention, treatment and maintenance approaches by recognizing contraindications, risk factors, adverse events and complications, when applying compression therapy for venous leg ulcer patients. A literature review was conducted of current guidelines on venous leg ulcer prevention, management and maintenance.
Results
Searches took place from 29th February 2016 to 30th April 2016 and were prospectively limited to publications in the English and German languages and publication dates were between January 2009 and April 2016. Twenty Guidelines, clinical pathways and consensus papers on compression therapy for venous leg ulcer treatment and for venous disease, were included. Guidelines agreed on the following absolute contraindications: Arterial occlusive disease, heart failure and ankle brachial pressure index (ABPI) <0.5, but gave conflicting recommendations on relative contraindications, risks and adverse events. Moreover definitions were unclear and not consistent.
Conclusions
Evidence‐based guidance is needed to inform clinicians on risk factor, adverse effects, complications and contraindications. ABPI values need to be specified and details should be given on the type of compression that is safe to use. Ongoing research challenges the present recommendations, shifting some contraindications into a list of potential indications. Complications of compression can be prevented when adequate assessment is performed and clinicians are skilled in applying compression.
Cold atmospheric plasma (CAP, i.e. ionized air) is an innovating promising tool in reducing bacteria.
We conducted the first clinical trial with the novel PlasmaDerm® VU-2010 device to assess safety ...and, as secondary endpoints, efficacy and applicability of 45 s/cm(2) cold atmospheric plasma as add-on therapy against chronic venous leg ulcers.
From April 2011 to April 2012, 14 patients were randomized to receive standardized modern wound care (n = 7) or plasma in addition to standard care (n = 7) 3× per week for 8 weeks. The ulcer size was determined weekly (Visitrak® , photodocumentation). Bacterial load (bacterial swabs, contact agar plates) and pain during and between treatments (visual analogue scales) were assessed. Patients and doctors rated the applicability of plasma (questionnaires).
The plasma treatment was safe with 2 SAEs and 77 AEs approximately equally distributed among both groups (P = 0.77 and P = 1.0, Fisher's exact test). Two AEs probably related to plasma. Plasma treatment resulted in a significant reduction in lesional bacterial load (P = 0.04, Wilcoxon signed-rank test). A more than 50% ulcer size reduction was noted in 5/7 and 4/7 patients in the standard and plasma groups, respectively, and a greater size reduction occurred in the plasma group (plasma -5.3 cm(2) , standard: -3.4 cm(2) ) (non-significant, P = 0.42, log-rank test). The only ulcer that closed after 7 weeks received plasma. Patients in the plasma group quoted less pain compared to the control group. The plasma applicability was not rated inferior to standard wound care (P = 0.94, Wilcoxon-Mann-Whitney test). Physicians would recommend (P = 0.06, Wilcoxon-Mann-Whitney test) or repeat (P = 0.08, Wilcoxon-Mann-Whitney test) plasma treatment by trend.
Cold atmospheric plasma displays favourable antibacterial effects. We demonstrated that plasma treatment with the PlasmaDerm® VU-2010 device is safe and effective in patients with chronic venous leg ulcers. Thus, larger controlled trials and the development of devices with larger application surfaces are warranted.
Venous leg ulcers are the most common cause of chronic leg wounds, accounting for up to 70 % of all chronic leg ulcers and carrying with them a significant morbidity, especially for elderly patients. ...Among people aged 65 years and older, the annual prevalence is 1.7 %. Billions of dollars per year are spent caring for patients with these often difficult-to-heal and sometimes recurrent chronic wounds. Chronic non-healing wounds of the lower extremities are susceptible to microbial invasion and can lead to serious complications, such as delayed healing, cellulitis, enlargement of wound size, debilitating pain, and deeper wound infections causing systemic illness. Recognition and treatment of the infected venous leg ulcer is an essential skill set for any physician caring for geriatric patients. Most physicians rely on subjective clinical signs and patient-reported symptoms in the evaluation of infected chronic wounds. The conventional bacterial culture is a widely available tool for the diagnosis of bacterial infection but can have limitations. Systemic antibiotics, as well as topical antiseptics and antibiotics, can be employed to treat and control infection and critical colonization. Better understanding of microbial biofilms in the wound environment have caused them to emerge as an important reason for non-healing and infection due to their increased resistance to antimicrobial, immunological, and chemical attack. A sound understanding of the microbial-host environment and its complexities, as well as the pathophysiology of venous hypertension, must be appreciated to understand the need for a multimodality approach to treating an infected venous leg ulcer. Other treatment measures are often required, in addition to systemic and topical antibiotics, such as the application of wound bandages, compression therapy, and wound debridement, which can hasten clearance of the infection and help to promote healing.
Background
Leg ulcers are open skin wounds on the lower leg that can last weeks, months or even years. Most leg ulcers are the result of venous diseases. First‐line treatment options often include ...the use of compression bandages or stockings.
Objectives
To assess the effects of using compression bandages or stockings, compared with no compression, on the healing of venous leg ulcers in any setting and population.
Search methods
In June 2020 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 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 by language, date of publication or study setting.
Selection criteria
We included randomised controlled trials that compared any types of compression bandages or stockings with no compression in participants with venous leg ulcers in any setting.
Data collection and analysis
At least two review authors independently assessed studies using predetermined inclusion criteria. We carried out data extraction, and risk‐of‐bias assessment using the Cochrane risk‐of‐bias tool. We assessed the certainty of the evidence according to GRADE methodology.
Main results
We included 14 studies (1391 participants) in the review. Most studies were small (median study sample size: 51 participants). Participants were recruited from acute‐care settings, outpatient settings and community settings, and a large proportion (65.9%; 917/1391) of participants had a confirmed history or clinical evidence of chronic venous disease, a confirmed cause of chronic venous insufficiency, or an ankle pressure/brachial pressure ratio of greater than 0.8 or 0.9. The average age of participants ranged from 58.0 to 76.5 years (median: 70.1 years). The average duration of their leg ulcers ranged from 9.0 weeks to 31.6 months (median: 22.0 months), and a large proportion of participants (64.8%; 901/1391) had ulcers with an area between 5 and 20 cm2. Studies had a median follow‐up of 12 weeks. Compression bandages or stockings applied included short‐stretch bandage, four‐layer compression bandage, and Unna's boot (a type of inelastic gauze bandage impregnated with zinc oxide), and comparator groups used included 'usual care', pharmacological treatment, a variety of dressings, and a variety of treatments where some participants received compression (but it was not the norm). Of the 14 included studies, 10 (71.4%) presented findings which we consider to be at high overall risk of bias.
Primary outcomes
There is moderate‐certainty evidence (downgraded once for risk of bias) (1) that there is probably a shorter time to complete healing of venous leg ulcers in people wearing compression bandages or stockings compared with those not wearing compression (pooled hazard ratio for time‐to‐complete healing 2.17, 95% confidence interval (CI) 1.52 to 3.10; I2 = 59%; 5 studies, 733 participants); and (2) that people treated using compression bandages or stockings are more likely to experience complete ulcer healing within 12 months compared with people with no compression (10 studies, 1215 participants): risk ratio for complete healing 1.77, 95% CI 1.41 to 2.21; I2 = 65% (8 studies with analysable data, 1120 participants); synthesis without meta‐analysis suggests more completely‐healed ulcers in compression bandages or stockings than in no compression (2 studies without analysable data, 95 participants).
It is uncertain whether there is any difference in rates of adverse events between using compression bandages or stockings and no compression (very low‐certainty evidence; 3 studies, 585 participants).
Secondary outcomes
Moderate‐certainty evidence suggests that people using compression bandages or stockings probably have a lower mean pain score than those not using compression (four studies with 859 participants and another study with 69 ulcers): pooled mean difference −1.39, 95% CI −1.79 to −0.98; I2 = 65% (two studies with 426 participants and another study with 69 ulcers having analysable data); synthesis without meta‐analysis suggests a reduction in leg ulcer pain in compression bandages or stockings, compared with no compression (two studies without analysable data, 433 participants). Compression bandages or stockings versus no compression may improve disease‐specific quality of life, but not all aspects of general health status during the follow‐up of 12 weeks to 12 months (four studies with 859 participants; low‐certainty evidence).
It is uncertain if the use of compression bandages or stockings is more cost‐effective than not using them (three studies with 486 participants; very low‐certainty evidence).
Authors' conclusions
If using compression bandages or stockings, people with venous leg ulcers probably experience complete wound healing more quickly, and more people have wounds completely healed. The use of compression bandages or stockings probably reduces pain and may improve disease‐specific quality of life. There is uncertainty about adverse effects, and cost effectiveness.
Future research should focus on comparing alternative bandages and stockings with the primary endpoint of time to complete wound healing alongside adverse events including pain score, and health‐related quality of life, and should incorporate cost‐effectiveness analysis where possible. Future studies should adhere to international standards of trial conduct and reporting.
Abstract Venous ulcer is a common vascular condition affecting 1% of the population, and a prevalence that increases with age. Venous ulcer is defined by the American Venous Forum as “a ...full-thickness defect of skin, most frequently in the ankle region, that fails to heal spontaneously and is sustained by chronic venous disease, based on venous duplex ultrasound testing.” The economic and social burden of this condition is significant to both the affected individual and the health care system. The recurrent nature of venous ulcers underscore the need for treatment of the underlying pathophysiology, that is, ambulatory venous hypertension produced by venous valve reflux alone or in conjunction with venous obstruction.
Summary
Background
Venous leg ulcers (VLUs) are typically painful and heal slowly. Compression therapy offers high healing rates; however, improvements are not usually sustained. Exercise is a ...low‐cost, low‐risk and effective strategy for improving physical and mental health. Little is known about the feasibility and efficacy of supervised exercise training used in combination with compression therapy patients with VLUs.
Objectives
To assess the feasibility of a 12‐week supervised exercise programme as an adjunct therapy to compression in patients with VLUs.
Methods
This was a two‐centre, two‐arm, parallel‐group, randomized feasibility trial. Thirty‐nine patients with venous ulcers were recruited and randomized 1 : 1 either to exercise (three sessions weekly) plus compression therapy or compression only. Progress/success criteria included exercise attendance rate, loss to follow‐up and patient preference. Baseline assessments were repeated at 12 weeks, 6 months and 1 year, with healing rate and time, ulcer recurrence and infection incidents documented. Intervention and healthcare utilization costs were calculated. Qualitative data were collected to assess participants’ experiences.
Results
Seventy‐two per cent of the exercise group participants attended all scheduled exercise sessions. No serious adverse events and only two exercise‐related adverse events (both increased ulcer discharge) were reported. Loss to follow‐up was 5%. At 12 months, median ulcer healing time was lower in the exercise group (13 vs. 34·7 weeks). Mean National Health Service costs were £813·27 for the exercise and £2298·57 for the control group.
Conclusions
The feasibility and acceptability of both the supervised exercise programme in conjunction with compression therapy and the study procedures is supported.
What's already known about this topic?
Almost 70% of all leg ulcers have a venous component.
Up to 30% of venous leg ulcers (VLUs) do not respond to compression alone, remain open after 1 year of treatment and need an average of 51 treatment visits to heal.
Adjunct therapies to compression are needed.
Exercise can form part of the therapeutic pathway, but evidence to determine whether exercise training has an effect on ulcer healing and quality of life is limited.
What does this study add?
The findings support the feasibility and acceptability of supervised exercise training as an adjunct therapy for adults with VLUs.
The preliminary data also support the potential effectiveness of exercise training in improving ulcer healing.
An appropriately powered, multicentre trial is required to confirm the clinical and cost‐effectiveness of the intervention.
Linked Comment: Ferris and Harding. Br J Dermatol 2018; 178:1005–1006.
Plain language summary available online
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