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Previous advances have identified immune pathways associated with inflammatory skin diseases, leading to the development of targeted therapies. However, there is a lack of molecular approaches that delineate these pathways at the individual patient level for personalized diagnostic and therapeutic guidance. Here, we conduct a cross-comparison of expression profiles from multiple inflammatory skin diseases to identify gene modules defining relevant immune pathways. Seven modules are identified, representing key immune pathways: Th17, Th2, Th1, Type I IFNs, neutrophilic, macrophagic, and eosinophilic. These modules allow the development of a molecular map with high diagnostic efficacy for inflammatory skin diseases and clinico-pathologically undetermined cases. Aligning dominant modules with treatment targets offers a rational framework for treatment selection, improving response rates in both treatment-naïve patients and non-responders to targeted therapies. Overall, our approach offers precision medicine for inflammatory skin diseases, utilizing transcriptional modules to support diagnosis and guide personalized treatment selection., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: We developed the Hospital-to-Home-Health Transition Quality (H3TQ) Index for skilled home healthcare (HH) agencies to identify threats to safe, high-quality care transitions in real time., Objective: Assess the validity of H3TQ in a large sample across diverse communities., Research Design: A survey of recently hospitalized older adults referred for skilled HH services and their HH provider at two large HH agencies in Baltimore, MD, and New York, NY., Subjects: There were five hundred eighty-seven participants (309 older adults, 141 informal caregivers, and 137 HH providers). Older adults, caregivers, and HH providers rated 747 unique transitions. Of these, 403 were rated by both the older adult/caregiver and their HH provider, whereas the remaining transitions were rated by either party., Measures: Construct, concurrent, and predictive validity were assessed via the overall H3TQ rating, correlation with the care transition measure (CTM), and the Medicare Outcome and Assessment Information Set (OASIS)., Results: Proportion of transitions with quality issues as identified by HH providers and older adults/caregivers, respectively; Baltimore 55%, 35%; NYC 43%, 32%. Older adults/caregivers across sites rated their transitions as higher quality than did providers (P<0.05). H3TQ summed scores showed construct validity with the CTM-3 and concurrent validity with OASIS measures. Summed H3TQ scores were not significantly correlated with 30-day ED visits or rehospitalization., Conclusions: The H3TQ identifies care transition quality issues in real-time and demonstrated construct and concurrent validity, but not predictive validity. Findings demonstrate value in collecting multiple perspectives to evaluate care transition quality. Implementing the H3TQ could help identify transition-quality intervention opportunities for HH patients., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Patients requiring skilled home health care (HH) after hospitalization are at high risk of adverse events. Human factors engineering (HFE) approaches can be useful for measure development to optimize hospital-to-home transitions., Objective: To describe the development, initial psychometric validation, and feasibility of the Hospital-to-Home-Health-Transition Quality (H3TQ) Index to identify patient safety risks., Methods: Development : A multisite, mixed-methods study at 5 HH agencies in rural and urban sites across the United States. Testing : Prospective H3TQ implementation on older adults' hospital-to-HH transitions. Populations Studied : Older adults and caregivers receiving HH services after hospital discharge, and their HH providers (nurses and rehabilitation therapists)., Results: The H3TQ is a 12-item count of hospital-to-HH transitions best practices for safety that we developed through more than 180 hours of observations and more than 80 hours of interviews. The H3TQ demonstrated feasibility of use, stability, construct validity, and concurrent validity when tested on 75 transitions. The vast majority (70%) of hospital-to-HH transitions had at least one safety issue, and HH providers identified more patient safety threats than did patients/caregivers. The most frequently identified issues were unsafe home environments (32%), medication issues (29%), incomplete information (27%), and patients' lack of general understanding of care plans (27%)., Conclusions: The H3TQ is a novel measure to assess the quality of hospital-to-HH transitions and proactively identify transitions issues. Patients, caregivers, and HH providers offered valuable perspectives and should be included in safety reporting. Study findings can guide the design of interventions to optimize quality during the high-risk hospital-to-HH transition., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Skilled home healthcare (HH) provided in-person care to older adults during the COVID-19 pandemic, yet little is known about the pandemic's impact on HH care transition patterns. We investigated pandemic impact on (1) HH service volume; (2) population characteristics; and (3) care transition patterns for older adults receiving HH services after hospital or skilled nursing facility (SNF) discharge., Methods: Retrospective, cohort, comparative study of recently hospitalized older adults (≥ 65 years) receiving HH services after hospital or SNF discharge at two large HH agencies in Baltimore and New York City (NYC) 1-year pre- and 1-year post-pandemic onset. We used the Outcome and Assessment Information Set (OASIS) and service use records to examine HH utilization, patient characteristics, visit timeliness, medication issues, and 30-day emergency department (ED) visit and rehospitalization., Results: Across sites, admissions to HH declined by 23% in the pandemic's first year. Compared to the year prior, older adults receiving HH services during the first year of the pandemic were more likely to be younger, have worse mental, respiratory, and functional status in some areas, and be assessed by HH providers as having higher risk of rehospitalization. Thirty-day rehospitalization rates were lower during the first year of the pandemic. COVID-positive HH patients had lower odds of 30-day ED visit or rehospitalization. At the NYC site, extended duration between discharge and first HH visit was associated with reduced 30-day ED visit or rehospitalization., Conclusions: HH patient characteristics and utilization were distinct in Baltimore versus NYC in the initial year of the COVID-19 pandemic. Study findings suggest some older adults who needed HH may not have received it, since the decrease in HH services occurred as SNF use decreased nationally. Findings demonstrate the importance of understanding HH agency responsiveness during public health emergencies to ensure older adults' access to care., (© 2024 The American Geriatrics Society.)

Epithelial skin cancers are extremely common, but the mechanisms underlying their malignant progression are still poorly defined. Here, we identify the NRF3 transcription factor as a tumor suppressor in the skin. NRF3 protein expression is strongly downregulated or even absent in invasively growing cancer cells of patients with basal and squamous cell carcinomas (BCC and SCC). NRF3 deficiency promoted malignant conversion of chemically induced skin tumors in immunocompetent mice, clonogenic growth and migration of human SCC cells, their invasiveness in 3D cultures, and xenograft tumor formation. Mechanistically, the tumor-suppressive effect of NRF3 involves HSPA5, a key regulator of the unfolded protein response, which we identified as a potential NRF3 interactor. HSPA5 levels increased in the absence of NRF3, thereby promoting cancer cell survival and migration. Pharmacological inhibition or knock-down of HSPA5 rescued the malignant features of NRF3-deficient SCC cells in vitro and in preclinical mouse models. Together with the strong expression of HSPA5 in NRF3-deficient cancer cells of SCC patients, these results suggest HSPA5 inhibition as a treatment strategy for these malignancies in stratified cancer patients., (© 2023 The Authors. Published under the terms of the CC BY 4.0 license.)

Objective: This study explored the key characteristics and needs of midlevel nurse managers (MLNMs) who support and engage clinical nurses (CNs) in scholarly inquiry., Background: Healthcare organizations expect CNs to participate in scholarly inquiry, incorporating evidence-based interventions to improve outcomes and safety. How the MLNM supports and engages CNs in scholarly inquiry remains unclear., Methods: Twelve semistructured interviews of MLNMs occurred at several facilities in the mid-Atlantic region utilizing the institutional review board-acknowledged protocol. Theme interpretation utilized inductive analysis., Results: Four recurrent themes emerged from the interviews related to the value of scholarly inquiry: 1) securing organizational resources to promote scholarly inquiry; 2) knowledge and experience in scholarly inquiry; 3) actions supporting scholarly inquiry; and 4) the value of scholarly inquiry within the organization., Conclusions: Senior nursing leadership and healthcare organizations must recognize the value and provide the infrastructure to support scholarly inquiry. Infrastructure includes education, dedicated time, access to expertise, and resources., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Patients discharged to the home on home-based outpatient parenteral antimicrobial therapy (OPAT) perform their own infusions and catheter care; thus, they require high-quality training to improve safety and the likelihood of treatment success. This article describes the study team's experience piloting an educational toolkit for patients on home-based OPAT., Methods: An OPAT toolkit was developed to address barriers such as unclear communication channels, rushed instruction, safe bathing with an intravenous (IV) catheter, and lack of standardized instructions. The research team evaluated the toolkit through interviews with home infusion nurses implementing the intervention, surveys of 20 patients who received the intervention, and five observations of the home infusion nurses delivering the intervention to patients and caregivers., Results: Of surveyed patients, 90.0% were comfortable infusing medications at the time of discharge, and 80.0% with bathing with the IV catheter. While all practiced on equipment, 75.0% used the videos and the paper checklists. Almost all (95.0%) were satisfied with their training, and all were satisfied with managing their IV catheters at home. The videos were considered very helpful, particularly as reference. Overall, nurses adjusted training to patient characteristics and modified the toolkit over time. Shorter instruction forms were more helpful than longer instruction forms., Conclusion: Developing a toolkit to improve the education of patients on home-based OPAT has the potential to improve the safety of and experience with home-based OPAT., (Copyright © 2022 The Joint Commission. Published by Elsevier Inc. All rights reserved.)

Primary cilium (PC) is a microtubule-based organelle found on the apical surface of most mammalian cell types, playing a role in development and tissue homeostasis. Ciliopathies are a rapidly growing group of human diseases characterized by disordered cilium. PC plays an important role in pathogenesis of basal cell cancer, the most common human malignancy. A significant increase in ciliation has been observed in the epidermis of atopic dermatitis and psoriasis patients. Spontaneously immortalized human keratinocytes, HaCaT are a model to study the epidermal homeostasis and pathophysiology. In contrast to what has been previously described, here, we show that HaCaT can be efficiently ciliated. In HaCaT cells, differentiation significantly increased the number of ciliated cells and we were able to analyse in detail the ciliary length progression with duration of differentiation. As the number of recognized ciliopathies continues to increase, the importance of ciliary models also rises. Even though keratinocytes do not become as highly and rapidly ciliated as cell lines frequently used in ciliary studies, they are a better model for the study of skin ciliopathies. Detailed progression of ciliation in HaCaT could serve as the basis for ciliary studies in this cell line., (© 2022 The Authors. Experimental Dermatology published by John Wiley & Sons Ltd.)

We evaluated the presence of tight junction (TJ) remnants in the stratum corneum (SC) of in vitro reconstructed human epidermis and human skin explants subjected or not to an aggressive topical treatment with beta-lipohydroxy salicylic acid (LSA) for 24 h. LSA-treated samples showed an increased presence of TJ remnants in the two lowermost layers of the SC, as quantified with standard electron microscopy. The topical aggression-induced overexpression of TJ-like cell-cell envelope fusions may influence SC functions: (1) directly, through an enhanced cohesion, and (2) indirectly, by impeding accessibility of peripheral corneodesmosomes to extracellular hydrolytic enzymes and, thus, slowing down desquamation. Observations of ichthyotic epidermis in peeling skin disease (PSD; corneodesmosin deficiency; two cases) and ichthyosis hypotrichosis sclerosing cholangitis syndrome (IHSC/NISCH; absence of claudin-1; two cases) also demonstrated increased persistence of TJ-like intercellular fusions in pathological SC and contributed to the interpretation of the diseases' pathological mechanisms.

Competing Interests: Competing interests: None.

Genodermatoses are rare inherited skin diseases that frequently affect other organs. They often have marked effects on wellbeing and may cause early death. Progress in molecular genetics and translational research has unravelled many underlying pathological mechanisms, and in several disorders with high unmet need, has opened the way for the introduction of innovative treatments. One approach is to intervene where cell-signaling pathways are dysregulated, in the case of overactive pathways by the use of selective inhibitors, or when the activity of an essential factor is decreased by augmenting a molecular component to correct disequilibrium in the pathway. Where inflammatory reactions have been induced by a genetically altered protein, another possible approach is to suppress the inflammation directly. Depending on the nature of the genodermatosis, the implicated protein or even on the particular mutation, to correct the consequences or the genetic defect, may require a highly personalised stratagem. Repurposed drugs, can be used to bring about a "read through" strategy especially where the genetic defect induces premature termination codons. Sometimes the defective protein can be replaced by a normal functioning one. Cell therapies with allogeneic normal keratinocytes or fibroblasts may restore the integrity of diseased skin and allogeneic bone marrow or mesenchymal cells may additionally rescue other affected organs. Genetic engineering is expanding rapidly. The insertion of a normal functioning gene into cells of the recipient is since long explored. More recently, genome editing, allows reframing, insertion or deletion of exons or disruption of aberrantly functioning genes. There are now several examples where these stratagems are being explored in the (pre)clinical phase of therapeutic trial programmes. Another stratagem, designed to reduce the severity of a given disease involves the use of RNAi to attenuate expression of a harmful protein by decreasing abundance of the cognate transcript. Most of these strategies are short-lasting and will thus require intermittent life-long administration. In contrast, insertion of healthy copies of the relevant gene or editing the disease locus in the genome to correct harmful mutations in stem cells is more likely to induce a permanent cure. Here we discuss the potential advantages and drawbacks of applying these technologies in patients with these genetic conditions. Given the severity of many genodermatoses, prevention of transmission to future generations remains an important goal including offering reproductive choices, such as preimplantation genetic testing, which can allow selection of an unaffected embryo for transfer to the uterus., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Morren, Legius, Giuliano, Hadj-Rabia, Hohl and Bodemer.)