Development of a core outcome set for use in research evaluations of interventions for venous leg ulceration: International eDelphi consensus.

INTRODUCTION: Venous leg ulceration (VLU) is a chronic, recurring condition with associated pain, malodour, impaired mobility and susceptibility to infection which in turn significantly impacts an individual's health-related quality of life. Randomised controlled trials (RCTs) aim to determine the efficacy of interventions to improve outcomes. To be useful, these outcomes should be consistently and fully reported across RCTs. A core outcome set (COS) is an agreed-upon standardised set of outcomes which should be, at a minimum, reported in all RCTs for a given indication including that of VLU. AIM: To gain consensus on which outcome domains and outcomes should be considered as core and therefore included in all RCTs of interventions in VLU treatment. METHOD: Two sequential, two round e-Delphi surveys were completed. The first gained consensus on core outcome domains and the second on core outcomes within those domains. Participants included: people with direct experience of having VLUs and their carers, healthcare professionals whose practice included VLU care and researchers within wound care (clinical, academic, industry). RESULTS: Five outcome domains; healing, pain, quality of life, resource use and adverse events, and 11 outcomes were rated as core by participants. The patient and not the limb or ulcer was the preferred unit of analysis for reporting. RECOMMENDATIONS: We recommend investigators report on all five outcome domains, regardless of the type of intervention being evaluated. Future research is needed to identify measurement methods for the 11 identified outcomes. We also recommend investigators follow the CONSORT guidelines (http://www.consort-statement.org/).

The effectiveness of interventions to improve the seasonal influenza vaccination uptake among nurses: A systematic review.

Background: Seasonal influenza is a significant cause of mortality and morbidity worldwide. Despite annual recommendations, influenza vaccination uptake rates are disproportionately lower among nurses compared to other health care professionals, especially when compared to physicians. Nurses have an additional risk of exposure to influenza infection due to the nature of their work. Aim: To determine the effectiveness of interventions in increasing seasonal influenza vaccination uptake among nurses. Methods: Evidence on the effectiveness of interventions to improve seasonal influenza vaccination uptake among nurses was systematically reviewed. A comprehensive search of six electronic databases and grey literature was undertaken. A minimum of two reviewers completed study selection, data extraction and risk of bias assessment independently. Results: One hundred and thirty-four studies were identified of which one cluster randomised trial met the inclusion criteria. The results of the included study found the implementation of an intervention with multiple components increased nurses' seasonal influenza vaccination rates during a single influenza season in geriatric healthcare settings in France. As the evidence in this review was very limited, it was not possible to make recommendations regarding which interventions were effective at increasing the seasonal influenza vaccination rate for nurses. Conclusion: This systematic review highlights a lack of high-quality studies that assessed interventions to improve the seasonal influenza vaccination of nurses. In view of the likelihood of influenza and the coronavirus (COVID-19) pandemic occurring together, it is imperative to have evidence on effective interventions for the nursing workforce and for policy decision makers.

Chronic wound-related pain, wound healing and the therapeutic potential of cannabinoids and endocannabinoid system modulation.

Chronic wounds represent a significant burden on the individual, and the healthcare system. Individuals with chronic wounds report pain to be the most challenging aspect of living with a chronic wound, with current therapeutic options deemed insufficient. The cutaneous endocannabinoid system is an important regulator of skin homeostasis, with evidence of system dysregulation in several cutaneous disorders. Herein, we describe the cutaneous endocannabinoid system, chronic wound-related pain, and comorbidities, and review preclinical and clinical evidence investigating endocannabinoid system modulation for wound-related pain and wound healing. Based on the current literature, there is some evidence to suggest efficacy of endocannabinoid system modulation for promotion of wound healing, attenuation of cutaneous disorder-related inflammation, and for the management of chronic wound-related pain. However, there is 1) a paucity of preclinical studies using validated models, specific for the study of chronic wound-related pain and 2) a lack of randomised control trials and strong clinical evidence relating to endocannabinoid system modulation for wound-related pain. In conclusion, while there is some limited evidence of benefit of endocannabinoid system modulation in wound healing and wound-related pain management, further research is required to better realise the potential of targeting the endocannabinoid system for these therapeutic applications.

Systematic review of topical interventions for the management of pain in chronic wounds.

Chronic wounds adversely affect quality of life. Pain is associated with chronic wounds, and its impact can vary according to wound aetiology, condition, and patient factors. This systematic review examined the effectiveness of topical interventions in the management chronic wound-related pain guided by PRISMA recommendations of randomised controlled trials (RCTs) where pain reduction is the primary outcome. Inclusion criteria were adults (older than 18 years) with chronic venous, arterial, diabetic, or pressure ulcers where pain has been managed through topical administration of pharmacological/nonpharmacological agents. Searches were conducted in Ovid Embase, Ovid MEDLINE, EBSCOhost, CINAHL, CENTRAL, PubMed, Web of Science, and Scopus. Studies were screened for eligibility; risk of bias and data were extracted by 2 independent assessors. Searches retrieved 10,327 titles and abstracts (7760 after deduplication). Nine full texts (1323 participants) examining ibuprofen (n = 4), morphine (n = 2), BWD + PHMB [polihexanide-containing biocellulose wound dressing] (n = 1), and EMLA (n = 2) were included. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool. Meta-analysis was not possible, but initial exploration suggests improved outcomes (reduced pain) for ibuprofen when compared with controls. Two studies involving morphine showed conflicting findings. Included studies often had small samples, and considering confounding factors (eg, comorbidities), the results should be interpreted with caution. Review of included studies suggests that topical interventions may provide pain relief in individuals with chronic wounds. Further adequately powered RCTs are recommended to assess the efficacy of topical interventions for the management of chronic wound-related pain.

Defining palliative wound care: A scoping review by European Association for Palliative Care wound care taskforce.

BACKGROUND: Deciding whether to transition to wound palliation is challenging for health care professionals because there is no agreed definition or understanding of palliative wound care, including the goals, core elements and differences from general wound management. OBJECTIVES: To conduct a scoping review with qualitative synthesis to define palliative wound care in terms of its conceptual framework, goals, principles, components, and differences from general wound management, and provide a new definition of palliative wound care based on this scoping review. ELIGIBILITY CRITERIA: Published literature that refers to the definitions, concept, goals and core elements of palliative wound care using any methodological approach, without any time limits, published in English. SOURCES OF EVIDENCE: The searches were conducted in CINAHL Complete via Ebsco, Medline via Ovid, Cochrane Library, Scopus, and Google Scholar. CHARTING METHODS: A data extraction form was developed by the review team and used independently for data charting purposes. Braun and Clarke's six phases of thematic analysis guided the qualitative synthesis. RESULTS: A total of 133 publications met the inclusion criteria. Three main themes were developed to define palliative wound care and understand its differences from general wound management: 1- Healing potential of wounds and patient vulnerability, 2- Understanding the impact on individuals and family to address needs, 3- Towards new goals and perspectives in approach to care. CONCLUSIONS: Palliative wound care focuses on symptom management, comfort, and dignity, but does not always target the healing of the wound, which is the goal of general wound care. The needs of the individual and their family must be addressed by clinicians through the provision of care and support that takes into account the true meaning of living and dying with a palliative wound. PROTOCOL REGISTRATION: A review protocol was developed but not registered.

Patients 'acceptance' of chronic wound-associated pain - A qualitative descriptive study.

Chronic wound-associated pain negatively impacts the quality of life of individuals and their families. To date, little research exists that has explored collectively how individuals describe wound pain, strategies they use to manage pain, and the perceived effectiveness of such strategies. Therefore, qualitative, semi-structured interviews were carried out between June and August 2021 with 13 individuals to gain a deeper understand of the experience and impact of chronic wound-associated pain in this population. Data were analyzed following Braun and Clarke's approach for reflexive thematic analysis using MAXQdA®. Two themes and subthemes were identified. Theme 1 reflects participants' characterization of pain and how wound-associated pain affected their daily life and how they learned to accept it. Participants felt functionally impaired. In theme 2, participants described how they accepted to live with such a pain even though they received support to manage their chronic wound-associated pain, especially during the dressing-changes. Patients depended on their health care professionals and family support networks to cope with the pain. Coping with pain is exhausting contributing to poorer quality of life. Health care professionals should be aware of wound-associated pain during dressing changes. Patients recommended the need for further research on dressings and not drugs to manage pain.

Prevalence and incidence of venous leg ulcers-A systematic review and meta-analysis.

Venous leg ulcers (VLU) represent a major public health challenge. Little is known about the prevalence and incidence of VLU internationally. Published studies are usually reporting different estimates because of disparities in study designs and measurement methods. Therefore, we conducted a systematic literature review and meta-analysis to identify the prevalence and incidence of VLU internationally and to characterise the population as reported in these studies. Studies were identified from searches in Medline (PubMed), CINAHL Complete (EBSCOhost), Embase, Scopus, Web of Science, LiSSa (Littérature Scientifique en Santé), Google Scholar and Cochrane Database of Systematic Reviews up to November 2022. Studies were included if their primary outcomes were reported as a period prevalence or point prevalence or cumulative incidence or incidence VLU rate. Fourteen studies met the inclusion criteria, 10 reporting estimates of prevalence, three reporting both prevalence and incidence estimates and one incidence. All were included in meta-analyses. The results show a pooled prevalence of 0.32% and a pooled incidence of 0.17%. Our results highlighted an extreme heterogeneity across effect sizes for both prevalence and incidence, which prevent a meaningful interpretation of pooled indexes and argue for further studies with specific prevalence-type reported and target population under study.

How health literacy relates to venous leg ulcer healing: A scoping review.

BACKGROUND: The level of personal health literacy of patients with venous leg ulcers is likely to affect their ability to self-manage their condition impacting on their adherence to treatment and influences healing and recovery outcomes. OBJECTIVES: To scope existing research that examined the level of health literacy in venous leg ulcer patients, to identify how this may link to self-management behaviours (particularly physical activity and compression adherence), and venous leg ulcer healing outcomes. METHODS: This scoping review was based on the PRISMA-ScR six-stage framework. We searched MEDLINE, EMBASE, the Cochrane Library, PsycInfo and Health, Open Grey, and Google Scholar for publications examining general and specific health literacy in those with venous leg ulcers and for those examining any potential links of health literacy with self-management/healing generally, published between 2000-2020. This search was guided by a published protocol; studies that described other types of ulcers or did not examine health literacy were excluded. After applying inclusion and exclusion criteria the initial search identified 660 articles. RESULTS: We included five articles. Four studies used randomised controlled trials or experimental designs to test the effect of specific health literacy interventions on venous leg ulcer knowledge, compression therapy use, or healing outcomes. One study was a cross- sectional survey with qualitative elements, assessing health literacy in venous leg ulcer patients. Broadly, the research suggested that health literacy was suboptimal amongst those with venous leg ulcers, and health literacy interventions had limited effects on improving key venous leg ulcer specific outcomes. CONCLUSION: This review provides a synthesis of extant literature examining health literacy in patients with venous leg ulcers. We identified a dearth of literature investigating the value of general and specific health literacy interventions in this space. Most importantly, no recent research on general health literacy and venous leg ulcers was identified, despite strong theoretical utility to do so. The few studies identified largely indicated that targeting health literacy of patients with venous leg ulcers is a viable area of research and intervention, encouraging future researchers and clinicians to consider patient health literacy in venous leg ulcer management.

Impact of hidradenitis suppurativa-specific wound dressing system on patient quality of life and dressing-related pain: pilot study.

OBJECTIVE: It is theorised that adhesive-free wound care developed specifically for patients with hidradenitis suppurativa (HS) can improve their quality of life (QoL). Our study aimed to investigate the impact of a novel wound care device on Dermatology Life Quality Index (DLQI) scores, and other factors related to experienced pain, time spent changing dressings, comfort, ease of use and body image. METHOD: A 21-day, single-arm, unblinded, pilot trial was conducted to assess ease of use and the impact of effective wound care on various aspects of wound management in patients with HS. Participants were provided two trial garments and trial dressings as required, to use over a 21-day period in the home setting. A seven-item questionnaire and the DLQI questionnaire was completed on days 0, 7, 14 and 21. RESULTS: All 15 participants were female, aged >18 years old and with a diagnosis of HS. Mean DLQI score at baseline (day 0) was 19.3, which was reduced to 4.53 on day 21, a significant improvement in 100% of participants (p<0.001). High levels of dressing-related pain, assessed using an 11-point Visual Analogue Scale, reduced from 5.53 at baseline to 0.8 on day 21. Other significant improvements in terms of patient comfort, time spent on changing dressings, body confidence and the dressing's ability to retain exudate were also noted. CONCLUSION: The results illustrated the improvement made to study participants' day-to-day activities and QoL when effective HS-specific wound care products were provided. Wound care is an essential component in the treatment journey of patients.

Topical interventions for the management of pain in chronic wounds: A protocol for a systematic review.

Background: Venous, arterial, diabetic and pressure ulcers, collectively known as chronic wounds, negatively impact individuals across psychological, social and financial domains. Chronic wounds can be painful and the nature, frequency and impact of pain can differ depending on wound aetiology, wound state and on numerous patient factors. While systemic pharmaceutical agents have some effect in managing pain, there is a need to examine topical agents applied to the wound bed for pain relief. The objective of this study is to examine and synthesise existing literature on the effectiveness of topical agents in managing pain in venous, diabetic, pressure, arterial and mixed venous/arterial ulcers. Methods: We will use Cochrane Systematic Review methodology to identify and synthesise eligible randomised controlled trials (RCTs) evaluating the effectiveness of topical agents in reducing pain in chronic wounds. Embase, Medline, PubMed, CENTRAL, CINAHL, Scopus and Web of Science will be searched from inception to end of June 2022 without language limits. We will independently extract data on the pharmaceutical agent, participant demographics, aetiology, condition of the wound, and type, nature and frequency of pain using a pre-designed data extraction form. Subgroup and sensitivity analysis will be performed to address heterogeneity across studies if appropriate. Further stratification and analyses will be based on included study variables and outcomes. Discussion: Wound pain is primarily managed via systemic pharmaceutical agents. However, patients express reluctance regarding systemic analgesic drugs, fearing addiction. Additionally, persons with chronic wounds have co-morbidities including hypertension, diabetes, or cardiovascular disease and are already taking multiple medications. Topical analgesia can potentially mitigate some of the perceived disadvantages of systemic agents but the available range of these agents and their effectiveness in managing pain in chronic wounds is not so well understood. This review will focus on such agents across a range of the most common chronic wounds.

Identifying outcomes reported in trials of interventions in venous leg ulceration for a core outcome set development: A scoping review.

BACKGROUND: Venous leg ulceration is a chronic, recurring, condition causing significant patient morbidity. Randomised controlled trials evaluating treatments for venous leg ulceration provide evidence for clinical decision-making. For trial findings to be useful, outcomes measured need to be clinically meaningful, and consistently and fully reported across trials. A core outcome set is an agreed and standardised set of outcomes which should be, as a minimum, reported in all trials for a given indication. AIM: To identify the outcome domains and outcomes reported in trials of interventions for venous leg ulceration. METHODS: A scoping review of the literature was carried out. Randomised controlled trials within Cochrane systematic reviews looking at venous leg ulceration interventions and qualitative studies exploring venous leg ulceration were included. RESULTS: The review identified 807 outcomes from randomised controlled trials and 15 outcomes from qualitative studies, and these were grouped into 11 outcome domains: healing, patient reported symptoms, clinician reported symptoms, carer reported symptoms, life impacts, clinical signs, clinical measurement, performance of the intervention, resource use (supplies and clinician time) and adverse events. The outcome domain 'healing' included 111 outcomes, 'symptoms' 109, 'life impacts' 30, 'clinical signs' 88, 'clinical measurement' 184, 'performance of the intervention' 58, 'resource use' 52 and 'adverse events' 190. CONCLUSION: The scoping review identified a large number of outcomes (n = 822) across 11 related outcome domains, supporting the need for a core outcome set.

Promoting and Maintaining Skin Integrity in End-of-Life Care: A Systematic Review.

OBJECTIVE: To systematically review recommendations for promoting and maintaining skin integrity in end-of-life care and their level of evidence. DATA SOURCES: MEDLINE (PubMed interface), CINAHL (Cumulative Index to Nursing and Allied Health Literature), EMBASE, and The Cochrane Library were systematically searched using a combination of key terms including end-of-life care , skin care , skin hygiene , and skin cleansing . STUDY SELECTION: Articles were included if they (1) described skin care recommendations, including but not limited to the use of skin care products and interventions such as cleansing procedures; and (2) included adult patients who were expected to die within 12 months. There were no restrictions on study design, study setting, or language. Articles with a publication date before 2000 were excluded. DATA EXTRACTION: Two data extraction forms were developed. The first included information about the author, publication year, type of evidence, study topic, sample, sample size, setting, limitations of the study, level of evidence, and quality of the study. The second included recommendations for promoting and maintaining skin integrity in patients at the end of life. DATA SYNTHESIS: Because of methodological heterogeneity, results were synthesized narratively, and no meta-analysis was performed. CONCLUSIONS: The information contained in the recommendations will assist nurses in promoting and maintaining skin integrity in patients at the end of life. More research is needed on end-of-life skin care, with an emphasis on patient-centered, holistic strategies that improve patient well-being and quality of life. In most current research, recommendations are limited to literature reviews and level V evidence. Skin care must balance the promotion and maintenance of skin integrity, wound prevention, and management while promoting patient dignity and quality of life.

The Personal Impact of Daily Wound Care for Hidradenitis Suppurativa.

BACKGROUND: Recurring nodules, abscesses, and lesions characterise hidradenitis suppurativa (HS): a chronic, inflammatory skin disorder. Globally the prevalence of HS is estimated to be around 1% of the population. Leakage, pain, and odour from HS wounds require substantial management. Little is known of the personal burdens that routine wound management imposes on the patient. OBJECTIVES: To evaluate how routine HS wound management impacts patients in terms of the time spent changing dressings, the number of dressings required per day, pain experienced during dressing changes, and negative impact on various domains of their personal lives. METHODS: An anonymous online questionnaire was posted on closed social media patient support groups between April and May 2019. Pearson χ2 test was used to evaluate if Hurley stages influenced the personal impact of wound care routines on patients. Statistical significance was determined as p value <0.05. RESULTS: In total, 908 people from 28 countries responded. Of these, 81% (n = 734) reported that regular dressing changes negatively impacted on their quality of life. Most patients, 82% (n = 744), experience pain during dressing changes. 16% (n = 142) of patients required five or more dressings daily, and 12% (n = 108) spend over 30 min daily tending to wounds. Patients indicated high levels of dissatisfaction with currently available wound dressings. CONCLUSION: HS wound management imposes a substantial personal burden on patients. There is a clear unmet need for HS-specific wound dressings and wound care provisions, and a greater awareness of the condition and its impact is needed among clinicians.

Health literacy in people with venous leg ulcers: a protocol for scoping review.

INTRODUCTION: Chronic venous leg ulcer (VLU) healing is a complex clinical problem. It requires intervention from skilled, costly, multidisciplinary wound-care teams, working with patients to manage their care. Compression therapy has been shown to help heal venous ulcers and to reduce recurrence, with some evidence suggesting the value of exercise as well. These activities require health education and health literacy (HL) as patients must process, understand and consistently apply health information for successful self-management. Research suggests that those most vulnerable to VLUs also tend to have limited HL, but there have been no reviews examining the state of HL in patients with previous or active VLUs. This scoping review aims to examine the level of HL in VLU patients and how HL may link to self-management behaviours (particularly exercise and compression adherence), and their VLU healing generally. METHODS AND ANALYSIS: We will use Preferred Reporting Items for Systematic Reviews and Meta-Analyses Scoping Review guidelines and the Levac methodology framework to explore eligible papers that examine the effect of HL on their exercise and compression adherence. Electronic databases will be searched (MEDLINE, EMBASE, the Cochrane Library, PsycInfo and Health, OpenGray), examining for all papers on these subjects published between 2000 and 2020. All studies describing compression and or exercise during VLU management will be included. Study characteristics will be recorded; qualitative data will be extracted and evaluated. Quantitative data will be extracted and summarised. ETHICS AND DISSEMINATION: We will disseminate results through peer-reviewed publications. We will use data (ie, journal articles) from publicly available platforms; so, this study does not require ethical review. The consultation step will be carried out with patients, carers and health professionals as part of an established wound consumer group.

What is the "normal" wound bed temperature? A scoping review and new hypothesis.

Wound bed temperature measurement holds the potential to be a safe, easy to use, and low-cost tool to aid objective wound bed assessment, clinical decision making and improved patient outcomes. However, there is no consensus on the normal range of wound bed temperature in chronic wounds. We conducted a scoping review including any study type, from 2010 to 2020 in which chronic wound bed temperature was reported. Thirteen studies including 477 patients met our criteria. Venous ulcers (VLU) accounted for 46.5% (n = 222) of wounds; diabetic foot ulcers (DFU) for 25.4% (n = 121) with pressure ulcers (PU), mixed arterial venous ulcers (MAVLU) and unknown aetiology accounting for the remainder. The weighted mean of means for wound bed temperature was 31.7°C (n = 395) for all wound types; 31.7°C for VLU; 31.6°C for DFU; 33.3°C for PU; 30.9°C for MAVLU; and 32.0°C for those with unknown aetiology. Based on our review, we hypothesise that normal wound bed temperature is within a range of 30.2-33.0°C.

Development of a core outcome set for venous leg ulceration (CoreVen) research evaluations (protocol).

BACKGROUND: A venous leg ulcer is a chronic leg wound caused by poor venous blood circulation in the lower limbs. It is a recurring condition causing pain, malodour, reduced mobility, and depression. Randomised controlled trials evaluating treatments for venous leg ulcers provide important evidence to inform clinical decision-making. However, for findings to be useful, outcomes need to be clinically meaningful, consistently reported across trials, and fully reported. Research has identified the large number of outcomes reported in venous leg ulcer trials, impacting both synthesis of results, and clinical decision-making. To address this, a core outcome set will be developed. A core outcome set is an agreed standardised set of outcomes which should be, as a minimum, measured and reported in all trials which evaluate treatment effectiveness for a given indication. A core outcome set has the potential to reduce research waste, improve the utility of RCTs, reduce reporting bias, facilitate treatment comparisons across different sources of evidence and expedite the production of systematic reviews, meta-analyses and evidence-based clinical guidelines. AIM: The aim of this project is to develop a core outcome set for research evaluating the effectiveness of interventions for treating venous leg ulceration. METHODS: Through a scoping review of the literature on venous leg ulceration, we will firstly identify a list of candidate outcome domains (broad categories in relation to what is being measured) from randomised controlled trials and qualitative research, and outcomes (specific methods in relation to what is being measured). In two further stages, we will use the resulting lists of outcome domains and outcomes to design two online surveys. A range of stakeholders will be invited to participate in the surveys and they will be asked to indicate which outcome domains and outcomes are most important and should be considered as core in future research reports.

Toward Developing Immunocompetent Diabetic Foot Ulcer-on-a-Chip Models for Drug Testing.

Bioengineering of skin has been significantly explored, ranging from the use of traditional cell culture systems to the most recent organ-on-a-chip (OoC) technology that permits skin modeling on physiological scales among other benefits. This article presents key considerations for developing physiologically relevant immunocompetent diabetic foot ulcer (DFU) models. Diabetic foot ulceration affects hundreds of millions of individuals globally, especially the elderly, and constitutes a major socioeconomic burden. When DFUs are not treated and managed in a timely manner, 15-50% of patients tend to undergo partial or complete amputation of the affected limb. Consequently, at least 40% of such patients die within 5 years postamputation. Currently, therapeutic strategies are actively sought and developed. However, present-day preclinical platforms (animals and in vitro models) are not robust enough to provide reliable data for clinical trials. Insights from published works on immunocompetent skin-on-a-chip models and bioengineering considerations, presented in this article, can inform researchers on how to develop robust OoC models for testing topical therapies such as growth factor-based therapies for DFUs. We propose that immunocompetent DFU-on-a-chip models should be bioengineered using diseased cells derived from individuals; in particular, the pathophysiological contribution of macrophages in diabetic wound healing, along with the typical fibroblasts and keratinocytes, needs to be recapitulated. The ideal model should consist of the following components: diseased cells embedded in reproducible scaffolds, which permit endogenous "diseased" extracellular matrix deposition, and the integration of the derived immunocompetent DFU model onto a microfluidic platform. The proposed DFU platforms will eventually facilitate reliable and robust drug testing of wound healing therapeutics, coupled with reduced clinical trial failure rates. Impact statement Current animal and cell-based systems are not physiologically relevant enough to retrieve reliable results for clinical translation of diabetic foot ulcer (DFU) therapies. Organ-on-a-chip (OoC) technology offers desirable features that could finally enable the vision of modeling DFU for pathophysiological studies and drug testing at a microscale. This article brings together the significant recent findings relevant to developing a minimally functional immunocompetent DFU-on-a-chip model, as wound healing cannot occur without a proper functioning immune response. It looks feasible in the future to recapitulate the stagnant inflammation in DFU (thought to impede wound healing) using OoC, diseased cells, and an endogenously produced extracellular matrix.

Psychological interventions for treating foot ulcers, and preventing their recurrence, in people with diabetes.

BACKGROUND: Diabetic foot ulceration (DFU) can be defined as a full-thickness wound below the ankle and is a major complication of diabetes mellitus. Despite best practice, many wounds fail to heal, and when they do, the risk of recurrence of DFU remains high. Beliefs about personal control, or influence, on ulceration are associated with better engagement with self-care in DFU. Psychological interventions aim to reduce levels of psychological distress and empower people to engage in self-care, and there is some evidence to suggest that they can impact positively on the rate of wound healing. OBJECTIVES: To evaluate the effects of psychological interventions on healing and recurrence of DFU. SEARCH METHODS: In September 2019, 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, Ovid PsycINFO and EBSCO CINAHL Plus. We also searched clinical trials registries for ongoing and unpublished studies, and reviewed reference lists of relevant included studies as well as reviews, meta-analyses and health technology reports to identify additional studies. There were no restrictions with respect to language, date of publication or study setting. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs that evaluated psychological interventions compared with standard care, education or another psychological intervention. Our primary outcomes were the proportion of wounds completely healed; time to complete wound healing; time to recurrence and number of recurrences. DATA COLLECTION AND ANALYSIS: Four review authors independently screened titles and abstracts of the studies identified by the search strategy for eligibility. Three authors independently screened all potentially relevant studies using the inclusion criteria and carried out data extraction, assessment of risk of bias and GRADE assessment of the certainty of the evidence. MAIN RESULTS: We identified seven trials that met the inclusion criteria with a total of 290 participants: six RCTs and one quasi-RCT. The studies were conducted in Australia, the USA, the UK, Indonesia, Norway and South Africa. Three trials used a counselling-style intervention and one assessed an intervention designed to enhance an understanding of well-being. One RCT used a biofeedback relaxation training intervention and one used a psychosocial intervention based on cognitive behavioural therapy. A quasi-RCT assessed motivation and tailored the intervention accordingly. Due to the heterogeneity of the trials identified, pooling of data was judged inappropriate, and we therefore present a narrative synthesis. Comparisons were (1) psychological intervention compared with standard care and (2) psychological intervention compared with another psychological intervention. We are uncertain whether there is a difference between psychological intervention and standard care for people with diabetic foot ulceration in the proportion of wounds completely healed (two trials, data not pooled, first trial RR 6.25, 95% CI 0.35 to 112.5; 16 participants, second trial RR 0.59, 95% CI 0.26 to 1.39; 60 participants), in foot ulcer recurrence after one year (two trials, data not pooled, first trial RR 0.67, 95% CI 0.32 to 1.41; 41 participants, second trial RR 0.63, 95% CI 0.05 to 7.90; 13 participants) or in health-related quality of life (one trial, MD 5.52, 95% CI -5.80 to 16.84; 56 participants). This is based on very low-certainty evidence which we downgraded for very serious study limitations, risk of bias and imprecision. We are uncertain whether there is a difference in the proportion of wounds completely healed in people with diabetic foot ulceration depending on whether they receive a psychological intervention compared with another psychological intervention (one trial, RR 2.33, 95% CI 0.92 to 5.93; 16 participants). This is based on very low-certainty evidence from one study which we downgraded for very serious study limitations, risk of bias and imprecision. Time to complete wound healing was reported in two studies but not in a way that was suitable for inclusion in this review. One trial reported self-efficacy and two trials reported quality of life, but only one reported quality of life in a manner that enabled us to extract data for this review. No studies explored the other primary outcome (time to recurrence) or secondary outcomes (amputations (major or distal) or cost). AUTHORS' CONCLUSIONS: We are unable to determine whether psychological interventions are of any benefit to people with an active diabetic foot ulcer or a history of diabetic foot ulcers to achieve complete wound healing or prevent recurrence. This is because there are few trials of psychological interventions in this area. Of the trials we included, few measured all of our outcomes of interest and, where they did so, we judged the evidence, using GRADE criteria, to be of very low certainty.