Comparative Analysis of Autologous Skin Cell-suspension Technology and Split-thickness Skin Grafting for Subacute Wounds in Medically Complex Patients: Propensity-Matched Cohort Study.

BACKGROUND: Non-healing wounds are particularly prevalent in older adults and in patients with multiple comorbidities and represent a significant medico-economic burden. Autologous split-thickness skin grafts (STSG) are considered the gold standard for wound closure but suffer from high failure rates and complications. Autologous skin cell-suspension (ASCS) technology is an autografting technique able to significantly minimize donor site morbidity. This retrospective, propensity-matched cohort study compared outcomes of wounds treated with ASCS versus STSG. STUDY DESIGN: Seven patients treated with ASCS were propensity-matched to 7 control patients who received STSG according to age and gender. The ASCS was prepared using the RECELL System and applied either alone as spray only ("ASCS alone", off-label) or combined with a widely meshed STSG ("ASCS+STSG", 3:1). The primary outcome was time to complete wound healing. Secondary outcomes included donor site healing, pain, and total number of visits. Statistical analyses included descriptive statistics, univariate analyses, and mixed-effect regression modeling to assess the impact of treatment on wound healing. RESULTS: A total of 14 patients and 17 wounds (10 treatment vs 7 control) were included. Demographics were well-matched between cohorts. The overall mean wound healing time was 85.6±11.2 days. Wounds treated with ASCS (both ASCS groups) healed faster than STSG (75.9±4.5 vs 99.4±26.7 days). Wounds treated with ASCS alone healed in 80.8±5.1 days, while those treated with ASCS and STSG healed in 68.5±7.6 days. CONCLUSIONS: This study suggests ASCS may offer clinically significant improvements in wound and donor site healing, with significantly less donor skin requirements, and comparable pain levels, compared to traditional STSG. Further research with a prospective study and larger sample size is needed to validate these findings.

Healthcare workers' mental health during the COVID-19 pandemic: a qualitative analysis of a text message-based NHS workforce support line.

BACKGROUND: The National Health Service (NHS) is suffering from a workforce crisis of mental and physical sickness and attrition following the COVID-19 pandemic. An in-depth understanding of healthcare workers' (HCWs) experiences during the pandemic is required to understand the impacts on their mental health in this challenging work environment. This qualitative study explores HCWs' concerns during the COVID-19 pandemic-expressed in real time during an active mental health crisis. DESIGN: This study involved analysis of data from 'Shout', a text message-based, UK-wide mental health support service which, during the pandemic, was advertised to HCWs specifically. Pseudorandom sampling of scripts of anonymised text message conversations between HCWs and Shout Volunteers from April 2020 to March 2021 was undertaken, with data fully anonymised by Shout before researchers accessed them on a secure purpose-built platform. Following application of exclusion and inclusion criteria, 60 conversations were coded to develop a thematic framework and analysed using grounded theory, with subthemes triangulated to create final themes. Quotes extracted from this process were then synthesised for publication. RESULTS: Three themes emerged from the data: (1) poor mental health, subthemes-(a) overwhelming negative feelings or emotional distress experienced, and; (b) active crisis/resurgent symptoms. (2) Negative work experiences, subthemes: (a) negative NHS work culture and expectations; (b) inadequate structures and arrangements for support; (c) trauma at work, and (d) abuse at work. (3) The impact of the COVID-19 pandemic, subthemes: (a) additional work pressure and (b) isolation and risk. CONCLUSION: This study explores the challenges and mental health concerns in HCWs during an active crisis. Organisational stressors, mental health provision and additional resources for HCWs to recover from the pandemic remain a vital issue in current NHS service provision.

Hexasodium fytate for the treatment of calciphylaxis: a randomised, double-blind, phase 3, placebo-controlled trial with an open-label extension.

Background: In the CALCIPHYX trial, we investigated hexasodium fytate, an inhibitor of vascular calcification, for the treatment of calcific uraemic arteriolopathy (calciphylaxis), a rare condition characterised by painful, non-healing skin lesions. Methods: In this international, phase 3, randomised, double-blind, placebo-controlled trial, adults with an ulcerated calciphylaxis lesion and pain visual analogue scale (VAS) score ≥50/100 were randomised 1:1 to hexasodium fytate 7 mg/kg or placebo intravenously during maintenance haemodialysis. Primary efficacy outcomes were an 8-item modification of the Bates-Jensen Wound Assessment Tool (BWAT-CUA) and Pain VAS in the intention-to-treat population. ClinicalTrials.gov number: NCT04195906. Findings: Overall, 34/37 patients randomised to hexasodium fytate and 26/34 patients randomised to placebo completed the 12-week randomised treatment period. At Week 12, both groups (hexasodium fytate versus placebo) showed similar improvements in BWAT-CUA (mean [standard deviation (SD)], -5.3 [5.2] versus -6.0 [6.2]; least squares mean difference, 0.3 [96% confidence interval (CI): -2.5, 3.0]; p = 0.88) and Pain VAS (mean [SD], -19.5 [26.9] versus -32.2 [38.5]; least squares mean difference, 11.5 [96% CI: -4.8, 27.8]; p = 0.15). One patient randomised to placebo briefly received hexasodium fytate in error. Serious adverse events through Week 12 included: calciphylaxis-related events leading to hospitalisation (2/38 [5%] versus 11/33 [33%]) and death (1/38 [3%] versus 5/33 [15%]). During the subsequent 12 weeks of open-label hexasodium fytate and 4 weeks of follow-up, there were no additional calciphylaxis-related events leading to hospitalisation. Over the course of the entire trial, deaths were 2/38 [5%] for the hexasodium fytate group and 7/33 [21%] for the placebo group. Interpretation: In patients with calciphylaxis, BWAT-CUA and Pain VAS improved similarly in hexasodium fytate- and placebo-treated patients; over the course of the entire trial, there were fewer deaths and calciphylaxis-related events leading to hospitalisation in the hexasodium fytate group. Funding: Funded by Sanifit, a CSL Vifor company.

Analysis of Biogenic Amines and Small Molecule Metabolites in Human Diabetic Wound Ulcer Exudate.

Diabetic foot ulcers (DFUs) pose a significant challenge in wound care due to their chronic nature and impaired healing processes. This study examines the biogenic amines and small molecule metabolites present in DFU wound exudates to identify their potential roles in wound healing. Under an IRB-approved protocol, wound fluid samples were collected from 25 diabetic patients and analyzed using ultrahigh-pressure liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry. The analysis identified 721 metabolites, with 402 confirmed through stringent criteria. Key metabolites significantly contributing to the wound exudates include betaine, lactic acid, carnitine, choline, creatine, and metformin (a widely used first-line treatment for type 2 diabetes). These molecules are known to influence wound healing processes, such as collagen synthesis, angiogenesis, inflammation modulation, and energy metabolism. Notably, the presence of drugs such as metformin and beclomethasone in the exudates suggests significant pharmacodynamic interactions that could influence wound healing. Specifically, we discovered that the combined use of insulin and metformin administered systemically significantly increased the concentration of metformin in the wound exudates (from 0.3% ± 0.0 to 3.1% ± 3.4; p = 0.00 49). This study highlights the complexity of DFU exudate composition and underscores the potential for targeted metabolic profiling to develop personalized wound care strategies.

Surgical Aspects of Wound Care in Older Adults.

The physical, emotional, and financial toll of acute and chronic nonhealing wounds on older adults and their caregivers is immense. Surgical treatment of wounds in older adults can facilitate healing but must consider the medical complexity of the patient, the patient's desires for treatment and the likelihood of healing. Innovative approaches and devices can promote rapid healing. By using a team approach, from preoperative planning to postoperative care, with a focus on the needs and desires of the patient, successful outcomes with improved patient satisfaction are possible even in medically complex patients.

Investigating Inflammatory Markers in Wound Healing: Understanding Implications and Identifying Artifacts.

Understanding the complex interplay of pro-inflammatory and anti-inflammatory cytokines is crucial in the field of wound healing, as it holds the key to developing effective therapeutics. In the initial stages of wound healing, pro-inflammatory cytokines like IL-1ß, IL-6, TNF-α, and various chemokines play vital roles in recruiting cells for debris clearance and the recruitment of growth factors. Careful regulation and timely resolution of this early inflammation are essential for optimal wound repair. As the healing process progresses, anti-inflammatory proteins such as IL-10 and IL-4 become instrumental in facilitating the transition to later stages where pro-inflammatory cytokines promote angiogenesis and wound remodeling. This Perspective underscores the complexity of inflammatory cytokines in wound healing research and emphasizes the need for comprehensive and unbiased methodologies in their evaluation. For robust and reliable results in wound-healing research, a more holistic approach is necessary-one that considers the roles, interactions, and timing of biological molecules, alongside careful sampling and evaluation strategies.

WHS guidelines for the treatment of pressure ulcers-2023 update.

The major populations at risk for developing pressure ulcers are older adults who have multiple risk factors that increase their vulnerability, people who are critically ill and those with spinal cord injury/disease. The reported prevalence of pressure ulcers in the United States is 2.5 million. However, this estimate is derived from acute care facilities and does not include people who are living at home or in nursing facilities. Despite the implementation of hospital and facility-based preventive measures, the incidence of pressure ulcers has not decreased in decades. In addition to the burden of pain, infection and death, it is estimated that hospital-acquired pressure ulcers cost the health system $26.8 billion annually with over 50% of the cost attributed to treating Stage 3 and 4 pressure injuries. Thus, it is critical to examine the literature and develop guidelines that will improve the outcomes of this complex and costly condition. This guideline update is a compendium of the best available evidence for the treatment of Pressure Ulcers published since the last update in 2015 and includes a new section based on changing demographics entitled 'Palliative wound care for seriously ill patients with pressure ulcers'. The overall goal of the Wound Healing Society Guideline project is to present clear, concise and commercial free guidelines that clinicians can use to guide care, that researchers can use to develop studies that will improve treatment and that both clinicians and researchers can use to understand the gaps in our knowledge base.

A core domain set for pyoderma gangrenosum trial outcomes: an international eDelphi and consensus study from the UPGRADE initiative.

BACKGROUND: Pyoderma gangrenosum (PG) is a rare ulcerative skin condition with no current standardized outcomes or outcome measures. With a rich investigational therapeutic pipeline, standardization of outcomes and improvement of data quality and interpretability will promote the appropriate and consistent evaluation of potential new therapies. Core outcome sets (COS) are agreed, standardized sets of outcomes that represent the minimum that should be measured and reported in all clinical trials of a specific condition. OBJECTIVES: To identify and reach a consensus on which domains (what to be measured) should be included in the Understanding Pyoderma Gangrenosum: Review and Analysis of Disease Effects (UPGRADE) core domain set for clinical trials in PG. METHODS: Collaborative discussions between patients and PG experts, and a systematic review of the literature identified items and prospective domains. A three-round international eDelphi exercise was performed to prioritize the domains and refine the provisional items (consensus: ≥ 70% of participants rating a domain as 'extremely important' and < 15% of participants voting 'not important'), followed by an international meeting to reach consensus on the core domain set (consensus: < 30% disagreement). Item-generation discussions and consensus meetings were hosted via online videoconferences. The eDelphi exercise and consensus voting were performed using Qualtrics survey software. Participants were adults with PG, healthcare professionals, researchers and industry representatives. RESULTS: Collaborative discussions and systematic reviews yielded 115 items, which were distilled into 15 prospective domains. The eDelphi exercise removed the three lowest-priority domains ('laboratory tests', 'treatment costs' and 'disease impact on family') and ranked 'pain', 'quality of life' and 'physical symptoms' as the highest-priority prospective domains. Consensus was reached on the domains of 'pain', 'quality of life' and 'clinical signs'. The domain of 'disease course/disease progression' narrowly failed to reach consensus for inclusion in the core set (32% of participants voted 'no'). Refinement of this domain definition will be required and presented for consideration at future consensus meetings. CONCLUSIONS: The UPGRADE core domain set for clinical trials in PG has been agreed by international multistakeholder consensus. Future work will develop and/or select outcome measurement instruments for these domains to establish a COS.

Eligibility Criteria for Active Ulcerative Pyoderma Gangrenosum in Clinical Trials: A Delphi Consensus on Behalf of the UPGRADE (Understanding Pyoderma Gangrenosum: Review and Assessment of Disease Effects) Group.

At present, there are no standardized guidelines for determining patient eligibility for pyoderma gangrenosum (PG) clinical trials. Thus, we aim to determine which clinical features, histopathological features, or laboratory features should be included in active ulcerative PG clinical trial eligibility criteria for treatment-naïve patients and patients already treated with immunomodulating medications (treatment-exposed patients). This study employed 4 rounds of the Delphi technique. Electronic surveys were administered to 21 international board-certified dermatologists and plastic surgeon PG experts (June 2022-December 2022). Our results demonstrated that for a patient to be eligible for a PG trial, they must meet the following criteria: (i) presence of ulcer(s) with erythematous/violaceous undermining wound borders, (ii) presence of a painful or tender ulcer, (iii) history/presence of rapidly progressing disease, (iv) exclusion of infection and other causes of cutaneous ulceration, (v) biopsy for H&E staining, and (vi) a presence/history of pathergy. These criteria vary in importance for treatment-naïve versus treatment-exposed patients. Given the international cohort, we were unable to facilitate live discussions between rounds. This Delphi consensus study provides a set of specific, standardized eligibility criteria for PG clinical trials, thus addressing one of the main issues hampering progress toward Food and Drug Administration approval of medications for PG.

Effect of tobacco smoking on outcomes of trabeculectomy / Efeito do tabagismo nos desfechos da trabeculectomia

ABSTRACT Purpose: To evaluate the effect of tobacco smoking on trabeculectomy outcomes. Methods: Charts of patients with glaucoma who underwent trabeculectomy performed by a single surgeon between 2007 and 2016 were retrospectively reviewed. Charts were screened for a documented history of smoking status before surgery. Demographic and clinical preoperative variables were recorded. Based on smoking history, subjects were divided into two groups: smokers and nonsmokers. Any bleb-related interventions (e.g., 5-flourouracil injections ± laser suture lysis) or bleb revision performed during the postoperative period were noted. Success was defined as an intraocular pressure >5 mmHg and <21 mm Hg without (complete success) or with (qualified success) the use of ocular hypotensive medications. Failure was identified as a violation of the criteria mentioned above. Results: A total of 98 eyes from 83 subjects were included. The mean age of the subjects was 70.7 ± 11.09 years, and 53% (44/83) were female. The most common diagnosis was primary open-angle glaucoma in 47 cases (47.9%). The smokers Group included 30 eyes from 30 subjects. When compared with nonsmokers, smokers had a significantly worse preoperative best-corrected visual acuity (p=0.038), greater central corneal thickness (p=0.047), and higher preoperative intraocular pressure (p=0.011). The success rate of trabeculectomy surgery at 1 year was 56.7% in the smokers Group compared with 79.4% in the Group nonsmokers (p=0.020). Smoking presented an odds ratio for failure of 2.95 (95% confidence interval, 1.6-7.84). Conclusion: Smokers demonstrated a significantly lower success rate 1 year after trabeculectomy compared with nonsmokers and a higher requirement for bleb-related interventions.

RESUMO Objetivo: Avaliar o efeito do tabagismo nos desfechos da trabeculectomia. Métodos: Uma revisão retrospectiva do gráfico de pacientes com glaucoma submetidos à trabeculectomia foi realizada por um único cirurgião entre 2007 e 2016. Os gráficos foram examinados para uma história documentada de condição de fumante antes da cirurgia. Variáveis pré-operatórias clínicas e demográficas e clínicas foram registradas. Os pacientes foram divididos em dois grupos de acordo com sua história de tabagismo em fumantes e não fumantes. Quaisquer Intervenções relacionadas à bolha, por exemplo, injeções de 5-fluorouracil + lise de sutura com laser, ou revisão da bolha realizada durante o período pós-operatório foram observadas. O sucesso foi definido como pressão intraocular > 5 mmHg e < 21 mm Hg sem (sucesso completo) ou com (sucesso qualificado) medicamentos hipotensores oculares. A falha foi identificada como violação dos critérios mencionados acima. Resultados: O estudo incluiu 98 olhos de 83 pacientes com idade média de 70,7 ± 11,09 anos, sendo 53% (44/83) dos pacientes do sexo feminino. O diagnóstico mais comum foi o glaucoma de ângulo aberto primário com 47 casos (47,9%). O Grupo de fumantes incluiu 30 olhos de 30 pacientes. Os fumantes, quando comparados aos não fumantes, apresentaram uma melhor acuidade visual pré-operatória significativamente pior (p=0,038), maior espessura central da córnea (p=0,047) e maior pressão intraocular pré-operatória (p=0,011). A taxa de sucesso de um ano para a cirurgia de trabeculectomia foi de 56,7% no Grupo de fumantes contra 79,4% no Grupo de não fumantes (p=0,020). O tabagismo apresentou razão de chances para falha de 2,95 95% de IC (1,6-7,84). Conclusão: Os fumantes demonstraram uma taxa de sucesso significativamente menor em um ano após a trabeculectomia em comparação com os não fumantes e uma maior necessidade de intervenções relacionadas à bolha.

Exploring the relationship between government stringency and preventative social behaviours during the COVID-19 pandemic in the United Kingdom.

We constructed a preventive social behaviours (PSB) Index using survey questions that were aligned with WHO recommendations, and used linear regression to assess the impact of reported COVID-19 deaths (RCD), people's confidence of government handling of the pandemic (CGH) and government stringency (GS) in the United Kingdom (UK) over time on the PSB index. We used repeated, nationally representative, cross-sectional surveys in the UK over the course of 41 weeks from 1st April 2020 to January 28th, 2021, including a total of 38,092 participants. The PSB index was positively correlated with the logarithm of RCD (R: 0.881, p < .001), CGH (R: 0.592, p < .001) and GS (R: 0.785, p < .001), but was not correlated with time (R: -0.118, p = .485). A multivariate linear regression analysis suggests that the log of RCD (coefficient: 0.125, p < .001), GS (coefficient: 0.010, p = .019), and CGH (coefficient: 0.0.009, p < .001) had a positive and significant impact on the PSB Index, while time did not affect it significantly. These findings suggest that people's behaviours could have been affected by multiple factors during the pandemic, with the number of COVID-19 deaths being the largest contributor towards an increase in protective behaviours in our model.

Chronic Wound Healing Models.

In this paper, we review and analyze the commonly available wound healing models reported in the literature and discuss their advantages and issues, considering their relevance and translational potential to humans. Our analysis includes different in vitro and in silico as well as in vivo models and experimental techniques. We further explore the new technologies in the study of wound healing to provide an all encompassing review of the most efficient ways to proceed with wound healing experiments. We revealed that there is not one model of wound healing that is superior and can give translatable results to human research. Rather, there are many different models that have specific uses for studying certain processes or stages of wound healing. Our analysis suggests that when performing an experiment to assess stages of wound healing or different therapies to enhance healing, one must consider not only the species that will be used but also the type of model and how this can best replicate the physiology or pathophysiology in humans.

Surgical Reconstruction of Stage 3 and 4 Pressure Injuries: A Literature Review and Proposed Algorithm from an Interprofessional Working Group.

OBJECTIVE: Stage 3 and 4 pressure injuries (PIs) present an enormous societal burden with no clearly defined interventions for surgical reconstruction. The authors sought to assess, via literature review and a reflection/evaluation of their own clinical practice experience (where applicable), the current limitations to the surgical intervention of stage 3 or 4 PIs and propose an algorithm for surgical reconstruction. METHODS: An interprofessional working group convened to review and assess the scientific literature and propose an algorithm for clinical practice. Data compiled from the literature and a comparison of institutional management were used to develop an algorithm for the surgical reconstruction of stage 3 and 4 PIs with adjunctive use of negative-pressure wound therapy and bioscaffolds. RESULTS: Surgical reconstruction of PI has relatively high complication rates. The use of negative-pressure wound therapy as adjunctive therapy is beneficial and widespread, leading to reduced dressing change frequency. The evidence for the use of bioscaffolds both in standard wound care and as an adjunct to surgical reconstruction of PI is limited. The proposed algorithm aims to reduce complications typically seen with this patient cohort and improve patient outcomes from surgical intervention. CONCLUSIONS: The working group has proposed a surgical algorithm for stage 3 and 4 PI reconstruction. The algorithm will be validated and refined through additional clinical research.

Minimizing bias in a diabetic foot ulcer clinical evaluation: analysis of the HIFLO Trial.

INTRODUCTION: Publications aimed at improving the quality of evidence in wound care clinical research have stressed the importance of minimizing study bias. In particular, lack of a universal definition of healing in wound studies leads to detection bias, resulting in noncomparable healing rates. OBJECTIVE: This report analyzes the steps taken to reduce the main sources of bias in a particular RCT (the HIFLO Trial) that evaluated healing in DFUs using microvascular tissue. MATERIALS AND METHODS: To address "definition of healing"-induced detection bias, 3 blinded adjudicators independently assessed each DFU using a rigorous 4-part definition of healing. Adjudicator responses were analyzed to assess reproducibility. Predefined criteria were also included to avoid bias owing to selection, performance, attrition, and reporting. RESULTS: Rigor and comparability across sites were ensured through investigator training, consistent SOC, data monitoring, and independent statistical and ITT-only analysis. The level of agreement among adjudicators was greater than or equal to 90% for each of the 4-part healing criteria. CONCLUSIONS: High-level agreement by blinded adjudicators confirmed that DFUs in the HIFLO Trial were consistently assessed for healing without bias, validating the most rigorous assessment criteria to date. The findings reported herein may prove beneficial for others seeking to minimize bias in wound studies.

The "Understanding Pyoderma Gangrenosum, Review and Assessment of Disease Effects (UPGRADE)" Project: a protocol for the development of the core outcome domain set for trials in pyoderma gangrenosum.

INTRODUCTION: Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis that affects approximately 0.3-6 out of every 100,000 people worldwide. Clinical trials are scarce but there is growing interest in using newer and more targeted therapeutics to achieve disease remission. However, there are no standardized instruments to measure outcomes in PG and, therefore, future clinical trials are hampered by the absence of established and accurate means of assessment and comparison. Therefore, we aim to produce an internationally accepted core outcome set (COS) that will overcome this obstacle. This protocol outlines our intended approach to achieve the first part of this process, establishing a core outcome domain set. METHODS: An international team of PG stakeholders, consisting of physicians, wound care nurses, patients, scientists and industry representatives, has been assembled for the purpose of building a comprehensive and universally established set of core outcome domains. During the first step, we will generate items of relevance using a nominal process from all stakeholders. Items will be distilled and collapsed into potential domains and subdomains. A systematic review of current methods for reporting PG has already been published and domains identified in this work will be considered in the generation of the core domains set. During the second step, after the potential domains and subdomains are identified, stakeholders will participate in an e-Delphi exercise to rate the importance of (sub)domains. A final consensus meeting will be organized with the goal of establishing a core domain set. CONCLUSION: Pyoderma gangrenosum lacks an established COS and previously published clinical trials have used inconsistent measures established from similarly inconsistent domains. As a first step this study seeks to create a core domain set within the COS, to build the foundation for future core outcome work for PG.

Effect of tobacco smoking on outcomes of trabeculectomy.

PURPOSE: To evaluate the effect of tobacco smoking on trabeculectomy outcomes. METHODS: Charts of patients with glaucoma who underwent trabeculectomy performed by a single surgeon between 2007 and 2016 were retrospectively reviewed. Charts were screened for a documented history of smoking status before surgery. Demographic and clinical preoperative variables were recorded. Based on smoking history, subjects were divided into two groups: smokers and nonsmokers. Any bleb-related interventions (e.g., 5-flourouracil injections ± laser suture lysis) or bleb revision performed during the postoperative period were noted. Success was defined as an intraocular pressure >5 mmHg and <21 mm Hg without (complete success) or with (qualified success) the use of ocular hypotensive medications. Failure was identified as a violation of the criteria mentioned above. RESULTS: A total of 98 eyes from 83 subjects were included. The mean age of the subjects was 70.7 ± 11.09 years, and 53% (44/83) were female. The most common diagnosis was primary open-angle glaucoma in 47 cases (47.9%). The smokers Group included 30 eyes from 30 subjects. When compared with nonsmokers, smokers had a significantly worse preoperative best-corrected visual acuity (p=0.038), greater central corneal thickness (p=0.047), and higher preoperative intraocular pressure (p=0.011). The success rate of trabeculectomy surgery at 1 year was 56.7% in the smokers Group compared with 79.4% in the Group nonsmokers (p=0.020). Smoking presented an odds ratio for failure of 2.95 (95% confidence interval, 1.6-7.84). CONCLUSION: Smokers demonstrated a significantly lower success rate 1 year after trabeculectomy compared with nonsmokers and a higher requirement for bleb-related interventions.

Chronic wounds: Treatment consensus.

The Wound Healing Foundation (WHF) recognised a need for an unbiased consensus on the best treatment of chronic wounds. A panel of 13 experts were invited to a virtual meeting which took place on 27 March 2021. The proceedings were organised in the sub-sections diagnosis, debridement, infection control, dressings, grafting, pain management, oxygen treatment, outcomes and future needs. Eighty percent or better concurrence among the panellists was considered a consensus. A large number of critical questions were discussed and agreed upon. Important takeaways included that wound care needs to be simplified to a point that it can be delivered by the patient or the patient's family. Another one was that telemonitoring, which has proved very useful during the COVID-19 pandemic, can help reduce the frequency of interventions by a visiting nurse or a wound care center. Defining patient expectations is critical to designing a successful treatment. Patient outcomes might include wound specific outcomes such as time to heal, wound size reduction, as well as improvement in quality of life. For those patients with expectations of healing, an aggressive approach to achieve that goal is recommended. When healing is not an expectation, such as in patients receiving palliative wound care, outcomes might include pain reduction, exudate management, odour management and/or other quality of life benefits to wound care.

'I'll put up with things for a long time before I need to call anybody': Face work, the Total Institution and the perpetuation of care inequalities.

Failures in fundamental care (e.g. nutrition or pain-relief) for hospitalised patients can have serious consequences, including avoidable deaths. Policy rhetoric of 'shared decision-making' fails to consider how structural constraints and power dynamics limit patient agency in nursing staff-patient interactions. Goffman's concepts of face work, the presentation of self and the Total Institution shaped our analysis of interview and focus group data from hospital patients. Patients avoided threatening 'good' patient and staff face by only requesting missed care when staff face was convincing as 'caring' and 'available' ('engaged'). Patients did not request care from 'distracted' staff ('caring' but not 'available'), whilst patient requests were ignored in Total Institution-like 'dismissive' interactions. This meant patients experienced missed care with both 'distracted' and 'dismissive' staff. Patients with higher support needs were less able to carry out their own missed care to protect staff face, so experienced more serious care omissions. These findings show that many elements of the Total Institution survive in modern healthcare settings despite attempts to support individualised care. Unless nursing staff can maintain face as 'engaged' (despite organisational constraints that can reduce their capacity to do so) patient participation in care decisions will remain at the level of rhetoric.

The CALCIPHYX study: a randomized, double-blind, placebo-controlled, Phase 3 clinical trial of SNF472 for the treatment of calciphylaxis.

BACKGROUND: Calcific uraemic arteriolopathy (CUA; calciphylaxis) is a rare disease seen predominantly in patients receiving dialysis. Calciphylaxis is characterized by poorly healing or non-healing wounds, and is associated with mortality, substantial morbidity related to infection and typically severe pain. In an open-label Phase 2 clinical trial, SNF472, a selective inhibitor of vascular calcification, was well-tolerated and associated with improvement in wound healing, reduction of wound-related pain and improvement in wound-related quality of life (QoL). Those results informed the design of the CALCIPHYX trial, an ongoing, randomized, placebo-controlled, Phase 3 trial of SNF472 for treatment of calciphylaxis. METHODS: In CALCIPHYX, 66 patients receiving haemodialysis who have an ulcerated calciphylaxis lesion will be randomized 1:1 to double-blind SNF472 (7 mg/kg intravenously) or placebo three times weekly for 12 weeks (Part 1), then receive open-label SNF472 for 12 weeks (Part 2). All patients will receive stable background care, which may include pain medications and sodium thiosulphate, in accordance with the clinical practices of each site. A statistically significant difference between the SNF472 and placebo groups for improvement of either primary endpoint at Week 12 will demonstrate efficacy of SNF472: change in Bates-Jensen Wound Assessment Tool-CUA (a quantitative wound assessment tool for evaluating calciphylaxis lesions) or change in pain visual analogue scale score. Additional endpoints will address wound-related QoL, qualitative changes in wounds, wound size, analgesic use and safety. CONCLUSIONS: This randomized, placebo-controlled Phase 3 clinical trial will examine the efficacy and safety of SNF472 in patients who have ulcerated calciphylaxis lesions. Patient recruitment is ongoing.