Effectiveness of interventions to enhance healing of chronic foot ulcers in diabetes: A systematic review.

BACKGROUND: It is critical that interventions used to enhance the healing of chronic foot ulcers in diabetes are backed by high-quality evidence and cost-effectiveness. In previous years, the systematic review accompanying guidelines published by the International Working Group of the Diabetic Foot performed 4-yearly updates of previous searches, including trials of prospective, cross-sectional and case-control design. AIMS: Due to a need to re-evaluate older studies against newer standards of reporting and assessment of risk of bias, we performed a whole new search from conception, but limiting studies to randomised control trials only. MATERIALS AND METHODS: For this systematic review, we searched PubMed, Scopus and Web of Science databases for published studies on randomised control trials of interventions to enhance healing of diabetes-related foot ulcers. We only included trials comparing interventions to standard of care. Two independent reviewers selected articles for inclusion and assessed relevant outcomes as well as methodological quality. RESULTS: The literature search identified 22,250 articles, of which 262 were selected for full text review across 10 categories of interventions. Overall, the certainty of evidence for a majority of wound healing interventions was low or very low, with moderate evidence existing for two interventions (sucrose-octasulfate and leucocyte, platelet and fibrin patch) and low quality evidence for a further four (hyperbaric oxygen, topical oxygen, placental derived products and negative pressure wound therapy). The majority of interventions had insufficient evidence. CONCLUSION: Overall, the evidence to support any other intervention to enhance wound healing is lacking and further high-quality randomised control trials are encouraged.

Guidelines on interventions to enhance healing of foot ulcers in people with diabetes (IWGDF 2023 update).

AIMS: Principles of wound management, including debridement, wound bed preparation, and newer technologies involving alternation of wound physiology to facilitate healing, are of utmost importance when attempting to heal a chronic diabetes-related foot ulcer. However, the rising incidence and costs of diabetes-related foot ulcer management necessitate that interventions to enhance wound healing of chronic diabetes-related foot ulcers are supported by high-quality evidence of efficacy and cost effectiveness when used in conjunction with established aspects of gold-standard multidisciplinary care. This is the 2023 International Working Group on the Diabetic Foot (IWGDF) evidence-based guideline on wound healing interventions to promote healing of foot ulcers in persons with diabetes. It serves as an update of the 2019 IWGDF guideline. MATERIALS AND METHODS: We followed the GRADE approach by devising clinical questions and important outcomes in the Patient-Intervention-Control-Outcome (PICO) format, undertaking a systematic review, developing summary of judgements tables, and writing recommendations and rationale for each question. Each recommendation is based on the evidence found in the systematic review and, using the GRADE summary of judgement items, including desirable and undesirable effects, certainty of evidence, patient values, resources required, cost effectiveness, equity, feasibility, and acceptability, we formulated recommendations that were agreed by the authors and reviewed by independent experts and stakeholders. RESULTS: From the results of the systematic review and evidence-to-decision making process, we were able to make 29 separate recommendations. We made a number of conditional supportive recommendations for the use of interventions to improve healing of foot ulcers in people with diabetes. These include the use of sucrose octasulfate dressings, the use of negative pressure wound therapies for post-operative wounds, the use of placental-derived products, the use of the autologous leucocyte/platelet/fibrin patch, the use of topical oxygen therapy, and the use of hyperbaric oxygen. Although in all cases it was stressed that these should be used where best standard of care was not able to heal the wound alone and where resources were available for the interventions. CONCLUSIONS: These wound healing recommendations should support improved outcomes for people with diabetes and ulcers of the foot, and we hope that widescale implementation will follow. However, although the certainty of much of the evidence on which to base the recommendations is improving, it remains poor overall. We encourage not more, but better quality trials including those with a health economic analysis, into this area.

Definitions and criteria for diabetes-related foot disease (IWGDF 2023 update).

Multiple disciplines are involved in the management of diabetes-related foot disease and a common vocabulary is essential for clear communication. Based on the systematic reviews of the literature that form the basis of the International Working Group on the Diabetic Foot (IWGDF) Guidelines, the IWGDF has developed a set of definitions and criteria for diabetes-related foot disease. This document describes the 2023 update of these definitions and criteria. We suggest these definitions be used consistently in both clinical practice and research, to facilitate clear communication with people with diabetes-related foot disease and between professionals around the world.

Guarana (Paullinia cupana Mart.) attenuates methylmercury-induced toxicity in Caenorhabditis elegans.

The influence of routine guarana (Paullinia cupana) consumption on apparent tolerance to mercury intoxication has been proposed. The present study investigated this hypothesis in Caenorhabditis elegans, a suitable experimental model for studies in toxicology. Wild type (WT) and skn-1 (ok2315) worm strains were pretreated with guarana ethanolic extract (GEE) from larvae 1 (L1) to L4 stage and then exposed for 6 hours to methylmercury (MeHg). The analyses included evaluation of GEE's effects on lethality, developmental delay, feeding, locomotion, gene expression (sod-3, gst-4, sir-2.1, hsf-1, snn-1, mtl-1, mtl-2, aat-1, aat-2 and aat-3) and antioxidant activity. GEE pre-treatment had no aberrant effects on WT worms exposed to MeHg, and protected skn-1 (ok2315) worms, which are more susceptible to environmental stresses. Protective effects of GEE might be dependent on modulation of genes other than those directly involved in antioxidant activity. GEE increased the expression of genes involved in metal transport (aat-2), metal detoxification (mtl-1 and mtl-2) and antioxidant responses (sir-2.1 and sod-3). Thus, routine consumption of guarana might be beneficial in protecting against MeHg-induced toxicity.

Predictors of long-term mortality in patients with ventilator-associated pneumonia.

PURPOSE: To determine the long-term outcome of ventilator-associated pneumonia (VAP) and identify factors associated with increased mortality. METHODS: We retrospectively studied 671 patients with VAP admitted to an intensive care unit between 1994 and 2000. We determined long-term and out-of-hospital mortality for these patients. RESULTS: The in-hospital mortality was 42.3%; 19.8% of patients had concomitant bacteremia, the mortality was 59.7% versus 38.0% for those without bacteremia (P <.001). The factors associated with increased hospital mortality by univariable analysis were: diagnosis on admission, the need of vasopressors during the stay in the intensive care unit, not undergoing a tracheostomy, the absence of fever, the presence of concomitant bacteremia, and renal failure or the need for dialysis. Patients transferred from an outside hospital and patients with normal serum bicarbonate, serum total bilirubin <2 mg/dL, and platelets >120x4> 10(3)/microL had a lower in-hospital mortality. All of these factors except bilirubin level, platelet count, transfer from outside hospital, and serum bicarbonate remained significant on multivariable analysis. The estimated mortality at 1, 3 and 5 years is 25.9% (95% confidence interval [CI], 20.2-30.1%), 33.6% (95% CI, 27.4-39.2%) and 44.7% (95% CI, 38.1-50.6%), respectively. CONCLUSIONS: VAP is associated with a high rate of hospital and long-term mortality. The presence of bacteremia is associated with a high mortality. The 5-year estimated mortality of the survivors is less than 50%.