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.

Skin Ulcers are Predictors of 30-Day Hospital Readmission, But are Under-represented in the DRG Coding: A Retrospective Case-Control Study From an Italian Internal Medicine Unit.

This study retrospectively analyzes all consecutive patients who underwent during a year hospital readmissions, defined as an admission to a hospital within 30 days of discharge, to an Italian Internal Medicine ward. All these data were compared with those from patients who underwent only 1 hospital admission in the same period. The aim of this study was to identify potential novel risk factors for hospital readmissions. In 2018, a total of 3012 patients were hospitalized. Among these, 14.1% (n = 426; mean age, 79.7 ± 11.9; range, 23-100) were defined as readmissions; data were compared with controls (n = 420; 13.9%; mean age, 75.9 ± 14.7; range, 22-99) who had only 1 hospitalization. Cases showed a significantly higher prevalence than controls regarding cerebrovascular disease (77.2% vs 48.1%), cognitive impairment (51.8% vs 26.9%), congestive heart failure (47.6% vs 20.2%), chronic kidney disease (31.7% vs 13.1%), and chronic obstructive pulmonary disease (23.0% vs 14.5%). Skin ulcers were significantly more prevalent among cases (45.1% vs 17.6%). Diagnosis-related group (DRG) analysis showed a higher proportion of "infectious disease" (24.4% vs 15.0%) among the cases than in controls. Despite skin ulcers were very frequent among cases and controls (45.1% vs 17.6%), they were codified as "skin wound" DRG only in 1.4% and 0.2%, respectively. At the DRGs analysis, sepsis (31.6% vs 19.1%), pneumonia (17.1% vs 7.6%), and kidney failure (9.6% vs 3.8%) represented the main significant cause of death in cases compared to controls. Our study confirms that readmissions to Internal Medicine departments are related to the severity of chronic diseases affecting patients. Skin ulcers are present in about half of patients who will be early readmitted within 30 days, but they are almost never reported in DRGs, so more accurate coding is needed. Key challenges for the future are sepsis prevention measures and investing resources in chronic disease assistance, including skin ulcer chronic management.

Multicenter Qualitative Study Exploring the Patient Experience of Digital Ulcers in Systemic Sclerosis.

OBJECTIVE: Digital ulcers (DUs) are a major cause of disease-related morbidity and are a difficult-to-treat vascular complication of systemic sclerosis (SSc). Demonstrating treatment efficacy has traditionally focused on clinician assessment of DUs alone. No existing patient-reported outcome (PRO) instrument captures the multifaceted impact of SSc-DU. We report the findings of a multicenter qualitative research study exploring the patient experience of SSc-DU. METHODS: Patient focus groups were conducted across 3 scleroderma units, following a topic guide devised by SSc patients, experts, and experienced qualitative researchers. A purposive sampling framework ensured that the experiences of a diverse group of patients were captured. Focus groups were audio recorded, and information was transcribed, anonymized, and analyzed using inductive thematic analysis. We continued focus groups until thematic saturation was achieved. RESULTS: Twenty-nine SSc patients with a history of DU disease participated in 4 focus groups across the UK (Bath, Manchester, and London). Five major interrelated themes (and subthemes) were identified that encompass the patient experience of SSc-DU: disabling pain and hypersensitivity; deep and broad-ranging emotional impact; impairment of physical and social activity; factors aggravating occurrence, duration, and impact; and mitigating, managing, and adapting. CONCLUSION: The patient experience of SSc-DU is multifaceted and comprises a complex interplay of experiences associated with significant pain and morbidity. Patient experiences of SSc-DU are not captured using existing SSc-DU outcomes. Our findings will inform the development of a novel PRO instrument to assess the severity and impact of SSc-DU for use in future SSc-DU clinical trials.

Digital ulcers in systemic sclerosis: their epidemiology, clinical characteristics, and associated clinical and economic burden.

BACKGROUND: To determine the frequency and clinical characteristics of systemic sclerosis-related digital ulcers, and associated direct health care costs, quality of life, and survival. METHODS: Digital ulcers (DUs) were defined as an area with a visually discernible depth and a loss of continuity of epithelial coverage. DU severity was calculated based on the physician reported highest number of new DUs at clinical review (mild = 1-5 DUs, moderate 6-10 DUs, severe > 10 DUs). Healthcare use was captured through data linkage, wherein SSc clinical data captured prospectively in a dedicated clinical database were linked with health services databases to capture hospital admissions, emergency department (ED) presentations and ambulatory care (MBS) utilization and cost for the period 2008-2015. Healthcare cost determinants were estimated using logistic regression. RESULTS: Among 1085 SSc patients, 48.6% experienced a DU over a mean follow-up of 5.2 ± 2.5 years. Those who developed DUs were more likely to have diffuse disease subtype (34.9% vs 18.2%, p < 0.001), anti-Scl-70 antibody (18.9% vs 9.3%, p < 0.001), and a younger age at SSc onset (43.6 ± 13.9 vs 48.8 ± 14.0 years, p < 0.001) in addition to reduced health-related quality of life (HRQoL) measured by the SF-36 but without a significant impact on survival. SSc patients with a history of a DU utilized significantly more healthcare resources per annum than those without a DU, including hospitalizations, ED presentation, and ambulatory care services. Total healthcare services, excluding medications, were associated with an annual excess cost per DU patient of AUD$12,474 (8574-25,677), p < 0.001, driven by hospital admission and ED presentation costs. CONCLUSION: DUs place a large burden on the patient and healthcare system through reduced HRQoL and increased healthcare resource utilization and associated cost.

Preliminary Validation of the Digital Ulcer Clinical Assessment Score in Systemic Sclerosis.

OBJECTIVE: To date, "healed/non-healed" and clinical judgment are the only available assessment tools for digital ulcers (DU) in patients with systemic sclerosis (SSc). The aim of our study is to examine a preliminary composite DU clinical assessment score (DUCAS) for SSc for face, content, and construct validity. METHODS: Patients with SSc presenting at least 1 finger DU were enrolled and assessed with the Health Assessment Questionnaire-Disability Index, Cochin scale, visual analog scale (VAS) for DU-related pain, patient global DU status, and global assessment as patient-reported outcomes (PRO), and physician VAS for DU status (phyGDU) as an SSc-DU expert physician/nurse measure. The DUCAS included 7 DU-related variables selected by a committee of SSc DU experts and weighted on a clinical basis. Face validity was examined by consensus and partial construct validity was tested through convergent correlation with other measures of hand function, using Spearman's correlations. A range of patients with SSc was examined. A linear regression model with backward stepwise analysis was used to determine the relationship of individual variables with the primary clinical parameter, phyGDU. RESULTS: Forty-four patients with SSc (9 males, mean age 55 ± 15 yrs, mean disease duration 9.9 ± 5.8 yrs) were enrolled in the study. Overall DUCAS showed significant positive correlations with all abovementioned PRO (r > 0.4, p < 0.01). When all scores and scales were modeled, only DUCAS significantly predicted phyGDU (r = 0.59, R2 = 0.354, Akaike information criterion = 385.4). CONCLUSION: Preliminarily, we suggest that the DUCAS may be a new clinical score for SSc-related DU, having face and content validity and convergent/divergent correlations (construct validity). These early data suggest that this score deserves further evaluation.

Hypoperfusion and Wound Healing: Another Dimension of Wound Assessment.

OBJECTIVE: To examine the correlation between mean arterial pressure (MAP) and wound healing indices and describe an analytical process that can be used accurately and prospectively when evaluating all types of skin ulcerations. METHODS: A correlational study in a long-term-care facility.Participants (N = 230) were adults residing in a long-term-care facility with an average age of 77.8 years (range, 35-105). MAIN OUTCOME MEASURES: Assessment through both an index of wound healing and wound surface area. Signs of wound healing included a reduction of surface area and surface necrosis and increased granulation or epithelialization. RESULTS: Aggregate analyses for all wound locations revealed a positive correlation between the MAP and index of wound healing (r = 0.86, n = 501, P < .0001). A well-defined positive correlation between the MAP and stalled or poor wound healing was noted for all wound locations in this data set when MAP values were 80 mm Hg or less (r = 0.95, n = 141, P < .0001). Further, the data set of truncal wounds and MAP of less than 80 mm Hg yielded a very strong positive correlation. The data indicated that as perfusion decreased, wounds within the sample population declined (r = 0.93, n = 102, P < .0001). CONCLUSION: The data suggest that MAP values less than 80 mm Hg can independently result in stalled wound healing or worsened wounds. A predictability of wounds stalling or declining related to the MAP was observed, regardless of topical treatment or standard-of-care interventions. Therefore, the data also suggest that remediating states of low perfusion should take precedence in making treatment decisions.

An observational cohort study of patients with newly diagnosed digital ulcer disease secondary to systemic sclerosis registered in the EUSTAR database.

OBJECTIVES: This study describes clinical characteristics, prognostic factors, and quality of life in patients with newly diagnosed (incident) digital ulcers (DU). METHODS: Observational cohort study of 189 consecutive SSc patients with incident DU diagnosis identified from the EUSTAR database (22 centres in 10 countries). Data were collected from medical charts and during one prospective visit between 01/2004 and 09/2010. RESULTS: Median age at DU diagnosis was 51 years, majority of patients were female (88%), and limited cutaneous SSc was the most common subtype (61%). At incident DU diagnosis, 41% of patients had one DU and 59% had ≥2 DU; at the prospective visit 52% had DU. Pulmonary arterial hypertension (PAH) and multiple DU at diagnosis were associated with presence of any DU at the prospective visit (odds ratios: 4.34 and 1.32). During the observation period (median follow-up was 2 years) 127 patients had ≥1 hospitalisation. The event rate of new DU per person-year was 0.66, of DU-associated complications was 0.10, and of surgical or diagnostic procedures was 0.12. At the prospective visit, patients with ≥1 DU reported impairment in daily activities by 57%, those with 0 DU by 37%. The mean difference between patients with or without DU in the SF-36 physical component was 2.2, and in the mental component 1.4. DU patients were not routinely prescribed endothelin receptor antagonists or prostanoids. CONCLUSIONS: This real world cohort demonstrates that DU require hospital admission, and impair daily activity. PAH and multiple DU at diagnosis were associated with future occurrence of DU.

The contribution of distance learning to the knowledge of nursing lecturers regarding assessment of chronic wounds.

OBJECTIVE: to identify the contribution made by a refresher course on the assessment of chronic wounds, offered through the Moodle virtual learning environment (VLE), to the knowledge relating to this issue of nursing lecturers and nurses linked to higher education. METHOD: a prospective, quasi-experimental study, with data collection before and after the educational intervention. The study was undertaken in three stages using the Moodle VLE. The sample was made up of 28 participants who answered the pre-test on the knowledge, devised in accordance with international guidelines on chronic wounds. Afterwards, the refresher course was offered (intervention) and was accessed in accordance with individuals' schedules, during the established time period. At the end of the course, 26 participants answered the post-test. Those who did not participate in the post-tests were excluded from the study, as it is pairwise analysis of the sample. RESULT: the participants obtained, on average, 55.5% of correct answers in the pre-test on their knowledge, and 73.4% in the post-test, this difference being statistically significant. There was a negative correlation between the time of experience in lecturing and the performance in the test on their knowledge. CONCLUSION: the participation in the online refresher course contributed to improving the lecturers' performance in the test on their knowledge, in relation to the recommendations for assessing chronic wounds, based in scientific evidence.

The relationship between nailfold capillaroscopic assessment and telangiectasia score with severity of peripheral vascular involvement in systemic sclerosis.

OBJECTIVES: To determine the association of nailfold video-capillaroscopy (NVC) findings and telangiectasia score with digital ulcer (DU) history and severity of peripheral vascular involvement (PVI) in systemic sclerosis (SSc). METHODS: Fifty-nine SSc patients fulfilling Leroy & Medsger criteria were evaluated including telangiectasia score, disease activity and severity scores. NVC was performed according to qualitative (early, active and late patterns) and semi-quantitative assessments. RESULTS: When DU+ and DU- groups were compared; the mean score of capillary number (CN) was 2.0±0.5 vs. 1.4±0.7 (p<0.001), irregularly enlarged capillaries (IEC) was 1.8±0.6 vs. 1.4±0.7 (p<0.05), microangiopathy evolution score (MES) was 2.5±1.5 vs. 1.8±1.0 (p<0.05) and 'early' pattern was significantly less frequent in DU+ patients (1 vs. 9, p=0.016). The frequency of severe-PVI (Medsger severity score of 2-4) was 22% in females (12/54) and 80% in males (4/5). When severe and non-severe groups were compared; the mean score of CN was 2.1±0.4 vs. 1.5±0.7 (p<0.001), MES was 2.8±1.6 vs. 1.8±1.1 (p<0.05) and 'early' pattern was significantly less frequent in patients with severe PVI (0 vs. 9, p=0.049). The mean values of telangiectasia score were similar between groups. CONCLUSIONS: DU history and severe PVI in SSc were associated with capillary loss and microangiopathy. 'Early' NVC pattern was very rare in patients with DU history and was not found in severe PVI. Severe PVI in males was more frequent than females. Telangiectasia scores were not found to be related to PVI. NVC may be a helpful method in the assessment of SSc patients for PVI prognosis, warranting prospective studies.

Assessment and documentation of non-healing, chronic wounds in inpatient health care facilities in the Czech Republic: an evaluation study.

The foundation of health care management of patients with non-healing, chronic wounds needs accurate evaluation followed by the selection of an appropriate therapeutic strategy. Assessment of non-healing, chronic wounds in clinical practice in the Czech Republic is not standardised. The aim of this study was to analyse the methods being used to assess non-healing, chronic wounds in inpatient facilities in the Czech Republic. The research was carried out at 77 inpatient medical facilities (8 university/faculty hospitals, 63 hospitals and 6 long- term hospitals) across all regions of the Czech Republic. A mixed model was used for the research (participatory observation including creation of field notes and content analysis of documents for documentation and analysis of qualitative and quantitative data). The results of this research have corroborated the suspicion of inconsistencies in procedures used by general nurses for assessment of non-healing, chronic wounds. However, the situation was found to be more positive with regard to evaluation of basic/fundamental parameters of a wound (e.g. size, depth and location of a wound) compared with the evaluation of more specific parameters (e.g. exudate or signs of infection). This included not only the number of observed variables, but also the action taken. Both were significantly improved when a consultant for wound healing was present (P = 0·047). The same applied to facilities possessing a certificate of quality issued by the Czech Wound Management Association (P = 0·010). In conclusion, an effective strategy for wound management depends on the method and scope of the assessment of non-healing, chronic wounds in place in clinical practice in observed facilities; improvement may be expected following the general introduction of a 'non-healing, chronic wound assessment' algorithm.

A Delphi exercise and cluster analysis to aid in the development of potential classification criteria for systemic sclerosis using SSc experts and databases.

OBJECTIVES: Since the 1980 ACR classification criteria for systemic sclerosis (SSc) do not identify 20% with SSc, revised criteria are necessary. METHODS: Suggested new criteria from the literature were sent in random order to 96 SSc experts. A 3-round Delphi Consensus eliminated criteria. Then cluster analysis reduced items. The Canadian Scleroderma Research Group (CSRG) database was used to determine the prevalence of each item. RESULTS: Seventy-one of 96 (71%) completed all 3 rounds; 47 items were expanded to 76 in round 2. Thirty items had at least 50% consensus and 18 had >75% agreement to include (a priori cut point). Clustering occurred for 4 categories: proximal to MCP skin involvement, vascular abnormalities, autoantibodies and tissue damage. Proximal to MCPs skin involvement identified 80% of patients. Adding one item from each of the other 3 categories or 1 or more items from 2 of 3 remaining categories increased the proportion of patients classified to 94% in CSRG patients. Categories included (1) Vascular (dilated capillaries, telangiectasia, Raynaud's phenomenon [RP]), (2) Autoantibodies (anticentromere [ACA] or antitopoisomeraseI [Topo1]) and (3) Fibrosis/damage (esophogeal dysmotility dysphagia, sclerodactyly, digital ulcers). In the CSRG, 98% were identified if using proximal skin involvement; or sclerodactyly plus one of: RP, ACA or Topo1. CONCLUSIONS: This is a first step toward developing new SSc classification criteria. A Delphi exercise alone cannot suffice for item reduction. Also, validation prospectively in SSc patients and diseases that mimic SSc is needed in order to calculate sensitivity and specificity of future criteria.

Evaluation of pH measurement as a method of wound assessment.

OBJECTIVE: To assess variations in wound pH levels and explore the relationship between wound pH and the state of wound healing. METHOD: Fifty patients with acute or chronic wounds attending the wound clinic at University Hospital,Varanasi, India were included. Wound pH was measured using litmus paper strips and recorded weekly. Other parameters recorded were the wound condition, exudate level and culture. RESULTS: The baseline pH of most of the wounds was greater than 8.5. As the wound condition improved and exudate levels decreased, the pH reduced to less than 8.0. Fifty-eight per cent of the wounds were culture positive, and an association was observed between the type of organism present and the wound pH. CONCLUSION: Wound pH measurements can be performed efficiently and are non-invasive, causing no discomfort to the patient. As the wounds healed, the pH reduced. This change in pH can help predict the likelihood of wound healing.

A stepwise approach to the laboratory diagnosis of Buruli ulcer disease.

OBJECTIVE: In view of technical and financial limitations in areas of endemicity, the current practice and recommendations for the laboratory diagnosis of Buruli ulcer disease (BUD) may have to be reconsidered. We reviewed diagnostic results in order to explore options for a modified, more practicable, cost-effective and timely approach to the laboratory diagnosis of BUD. METHODS: Diagnostic specimens from 161 clinically diagnosed BUD patients from four different treatment centres in Ghana were subjected to laboratory analysis. The positivity rates of the laboratory assays were compared. RESULTS: The number of laboratory-confirmed clinically diagnosed BUD cases with one positive confirmative test was 20% higher than that with two positive confirmative tests. The specificity of microscopy (MIC) and PCR was 96.6% and 100%, respectively. Subsequent analysis of specimens from surgically excised pre-ulcerative tissue-by-tissue MIC and tissue PCR rendered 65% laboratory-confirmed BUD cases. Subsequent analysis of diagnostic swabs from ulcerative lesions by swab smear MIC and swab PCR rendered 70% of laboratory-confirmed BUD cases. CONCLUSIONS: The specificity of the diagnostic tests used in this study suggests that one positive diagnostic test may be considered sufficient for the laboratory confirmation of BUD. Subsequent application of different diagnostic tests rendered a laboratory confirmation of 65% pre-ulcerative and of 70% ulcerative lesions. Implementation of a stepwise, subsequent analysis of diagnostic specimens will result in considerable cost saving compared with simultaneous testing of specimens by several diagnostic assays.