Does Accountability Affect Adherence to Moisturizer Treatment in Atopic Patients with Xerosis?

Introduction: Xerosis is common in atopic dermatitis (AD). Adherence depends on factors such as complexity of treatments, disease understanding and accountability. Accountability is a psychobehavioral construct, referring to the expectation that one must be responsible for their actions or inactions. Objective: We sought to assess whether interventions expected to improve accountability would be associated with improved adherence to xerosis treatment. Method: This is a prospective study of 30 patients diagnosed with xerosis . Patients were given moisturizer with an electronic monitor to record adherence and asked to apply it once daily for three months. Subjects were randomized into one of three arms: the control group (n=12), the electronic interaction group (n=10), or the GPSkin group (n=6). Electronic group received weekly email survey during the study to assess their Cetaphil use, while the GPSkin group received the GPSkin Barrier, a device that measures skin moisture and were instructed to obtain skin moisture measurements daily. Results: Mean adherence scores for the control was 56 (SD=25); electronic interaction group 34 (SD=39) and GPSkin group 19 (SD=19). Control group had higher adherence compared to the electronic interaction group (p=0.044), while no difference was observed between the control and GPSkin groups or between the electronic interaction and GPSkin groups (p=0.11 & p=0.83, respectively). Discussion: Weekly surveys and daily feedback on skin moisture did not appear to promote treatment adherence. This may be because these interactions did not involve direct social consequences, and therefore may not impact patients’ sense of accountability

The Clinical Definition and Characterization of Field of Cancerization in Patients with Actinic Keratoses

Introduction: Chronic UV radiation affects the entire area of skin exposed, leading to visible actinic keratoses (AK) and subclinical changes in the surrounding skin. AKs are hyperkeratotic lesions, with a 0.025-16% risk of transforming into squamous cell carcinoma (SCC).1 Cellular atypia around AKs is the field of cancerization (FOC). Topical AK therapies can treat the FOC, while destructive treatments address visible lesions. FDA-approved products may be approved for field sizes up to 25 cm2.1,2 Objective: To characterize the FOC and assess the correlation between the FOC and number of AKs. Methods: 100 patients with AKs were recruited. FOC was defined by a dermatologist. The size of the FOC was quantified to determine if FOC meets FDA-recommended AK topical treatment criteria. Results: 100 patients (mean age 71.2 years; 23% female) with AKs were enrolled, with 148 FOC. The mean AKs per field was 6.8 (SD=7.3). Mean size of the FOC was 75.3cm2 (SD=75). 111 of the 148 fields (75%) exceeded 25cm2. Number of AKs positively correlated with the size of the FOC. Mean FOC size and the mean number of AKs differed based on the body region affected (p=0.0337; p=0.0087). Conclusion: Cellular atypia changes due to UV radiation are important because if the surrounding area of atypia is not treated along with the visible AK, patients remain at risk for AK recurrence and progression to SCCs. Results suggest treating FOC of 25 cm2 may not be adequate for patients. AK therapy should consider FOC size, number of AKs, and patient preferences

Kinase inhibitors in the treatment of immune-mediated disease

Protein kinases are fundamental components of diverse signaling pathways, including immune cells. Their essential functions have made them effective therapeutic targets. Initially, the expectation was that a high degree of selectivity would be critical; however, with time, the use of “multikinase” inhibitors has expanded. Moreover, the spectrum of diseases in which kinase inhibitors are used has also expanded to include not only malignancies but also immune-mediated diseases. At present, thirteen kinase inhibitors have been approved in the United States, all for oncologic indications. However, there are a growing number of molecules, including several Janus kinase inhibitors, that are being tested in clinical trials for autoimmune diseases such as rheumatoid arthritis, psoriasis and inflammatory bowel diseases. It appears likely that this new class of immunomodulatory drugs will have a major impact on the treatment of immune-mediated diseases in the near future

Barriers to Dermatological Care in Patients who Received Extensive Mohs Surgery - An In-Depth Qualitative Analysis

Background: Dermatological care needs to be accessible for the elderly, but they face prominent challenges contributing to delays in diagnosis and treatment. Prolonged management of may lead to widespread cutaneous malignancies, necessitating extensive Mohs surgery. Objective: To identify areas for early intervention in the geriatric population who have undergone extensive Mohs surgery. Methods: We performed a qualitative study on 10 patients 65 years and older (68-91) from Atrium Health Wake Forest Baptist dermatology clinics between December 2022 and February 2023, who had extensive Mohs surgery (3 or more layers removed). Results: Three major areas for potential intervention for cutaneous carcinoma identified in our study were lack of knowledge, delayed care, and relationships. Discussion: Early cutaneous carcinoma intervention is essential to avoid extensive Mohs micrographic surgery and the associated risks, and to optimize patient health outcomes

Single-arm, open-label pilot intervention study to investigate an effect of oral 5-aminolevulinic acid plus sodium ferrous citrate on glucocorticoid reduction in patients with adult-onset Still disease

BACKGROUND: Glucocorticoids are an important class of medication for patients with adult-onset Still disease (AOSD), however, relapse following glucocorticoid reduction and adverse events due to long-term effects of glucocorticoid are still problematic. It is of course essential to minimize the risk of treatment. Immunosuppressive therapies such as methotrexate and biologics including tocilizumab are used in glucocorticoid-dependent patients with AOSD, but no second-line treatments for patients with glucocorticoid dependence have been established yet. Given that these drugs also have the potential to cause adverse events, alternative treatments are sought. Recently, elevated heme oxygenase-1 (HO-1) has been reported in the serum of patients with AOSD, suggesting that HO-1 activity contributes to AOSD pathogenesis and may represent a new therapeutic target for the treatment of AOSD. The amino acid 5-aminolevulinic acid (5-ALA) is a non-proteinogenic δ amino acid in human body. An addition of ferrous iron to 5-ALA enhances heme biosynthesis. The increase in heme in vivo induces HO-1 production, a heme-degrading enzyme. Elevated HO-1 has been suggested to contribute to the pathogenesis of AOSD, and administration of 5-ALA and ferrous iron may be a potential treatment for AOSD. METHODS/DESIGN: This study is a single-arm, open-label pilot intervention study using clinical endpoints to investigate the effects of oral 5-ALA with sodium ferrous citrate on glucocorticoid reduction in patients with AOSD receiving glucocorticoid therapy. DISCUSSION: This pilot intervention study will provide evidence regarding the effectiveness and safety of 5-ALA/sodium ferrous citrate as a potential new therapeutic agent for glucocorticoid-dependent patients with AOSD. TRIAL REGISTRATION: This study was registered in the Japan Registry of Clinical Trials (https://jrct.niph.go.jp) on January 14, 2020 as jRCTs071190042

Inhibition of the inositol kinase Itpkb augments calcium signaling in lymphocytes and reveals a novel strategy to treat autoimmune disease

Emerging approaches to treat immune disorders target positive regulatory kinases downstream of antigen receptors with small molecule inhibitors. Here we provide evidence for an alternative approach in which inhibition of the negative regulatory inositol kinase Itpkb in mature T lymphocytes results in enhanced intracellular calcium levels following antigen receptor activation leading to T cell death. Using Itpkb conditional knockout mice and LMW Itpkb inhibitors these studies reveal that Itpkb through its product IP4 inhibits the Orai1/Stim1 calcium channel on lymphocytes. Pharmacological inhibition or genetic deletion of Itpkb results in elevated intracellular Ca2+ and induction of FasL and Bim resulting in T cell apoptosis. Deletion of Itpkb or treatment with Itpkb inhibitors blocks T-cell dependent antibody responses in vivo and prevents T cell driven arthritis in rats. These data identify Itpkb as an essential mediator of T cell activation and suggest Itpkb inhibition as a novel approach to treat autoimmune disease

What is the future of targeted therapy in rheumatology: biologics or small molecules?

Background: Until late in the 20th century, the therapy of rheumatic diseases relied on the use of drugs that had been developed through empirical approaches without detailed understanding of the molecular mechanisms involved. That approach changed with the introduction of biologic therapeutics at the end of the 20th century and by the recent development of small-molecule inhibitors of intracellular signal transduction pathways. Here we compare and discuss the advantages and disadvantages of those two groups of targeted anti-inflammatory therapeutics.Discussion: TNF-blocking biologic agents were introduced into the therapy of rheumatoid arthritis and other autoimmune and inflammatory diseases in the late 1990s. Further biologic agents targeting cytokine networks or specific lymphocyte subsets have since been added to the armamentarium of anti-rheumatic therapy. During the last few years, another wave of novel discoveries led to the development of a new class of small molecule anti-inflammatory compounds targeting intracellular signal transduction molecules, such as tyrosine kinases. In all those cases, the specific targets of the drugs are well defined and significant knowledge about their role in the disease pathomechanism is available, qualifying them for being targeted therapeutics for inflammatory rheumatic diseases. While both groups of targeted therapeutics offer significant clinical benefit, they clearly differ in several aspects, such as the localization of their targets, their route of administration and target specificity, as well as technical details such as manufacturing procedures and cost basis. In this debate paper, we compare the advantages and disadvantages of the two different approaches, aiming to shed light on the possible future of targeted therapies.Summary: Biologic therapeutics and small-molecule inhibitors both have significant advantages and disadvantages in the therapy of rheumatic diseases. The future of targeted therapies is one of the most exciting questions of current rheumatology research and therapy. © 2014 Mócsai et al.; licensee BioMed Central Ltd

Χρηματοδοτική ναύλωση γυμνού σκάφους

Η ανάλυση που θα ακολουθήσει βρίσκεται στο μεταίχμιο του εμπορικού δικαίου, αποτελούμενη από στοιχεία τόσο του αμιγώς ναυτικού δικαίου όσο και του κλάδου των χρηματοοικονομικών. Η παρούσα έρευνα προσεγγίζει το θέμα της χρηματοδοτικής ναύλωσης γυμνού σκάφους, ως μέσο χρηματοδότησης στην απόκτηση πλοίων. Αρχικά εξετάζεται η έννοια της χρηματοδοτικής μίσθωσης και οι ειδικότερες εκφάνσεις της. Εν συνεχεία, διερευνώνται νομοθετικά ζητήματα του γυμνού πλοίου στην ελληνική έννομη τάξη, ενώ γίνεται μνεία των θετικών και αρνητικών επιδράσεων του θεσμού. Στο υπόλοιπο μέρος της μελέτης αναλύονται οι σχέσεις μεταξύ των συμβαλλομένων μερών και εκτίθενται διαδικαστικά ζητήματα σύναψης της εν λόγω σύμβασης, καθώς και ο μηχανισμός αφερεγγυότητας σχετικά με τα θέματα που αναφύονται για τη λειτουργία της ναυτιλιακής επιχείρησης. Σκοπός της παρούσας εκπόνησης, είναι να γίνει μια συνολική εποπτεία του ιδιάζοντος αυτού χρηματοδοτικού μέσου και να αναδειχθεί ο αντίκτυπός του στη σύγχρονη ναυτιλιακή βιομηχανία.The analysis that will follow is at the crossroads of commercial law, consisting of elements of both pure maritime law and the financial sector. This research approaches the issue of bare-boat chartering as a means of financing in ship acquisition. It first examines the concept of leasing and its more specific manifestations. Subsequently, legislative issues of naked ship leasing in the Greek legal order are explored, while the positive and negative effects of the institution are mentioned. The remainder of the study analyses the relations between the parties to the contract and sets out the procedural issues involved in the conclusion of the contract in question, as well as the insolvency mechanism relating to the issues arising for the operation of the shipping business. The purpose of this paper is to provide a comprehensive overview of this unique financial instrument and to highlight its impact on the modern shipping industry