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Background: Atopic dermatitis (AD) is a chronic condition with an increasing incidence in Japan. Difamilast and delgocitinib are both new topical drugs for AD proven to be efficacious and safe in phases 2 and 3 clinical trials in Japan. However, there are no head-to-head trials comparing their efficacy and safety. The aim of this study was to determine the proportion of patients by severity and compare the clinical efficacy and safety of difamilast with delgocitinib among patients with moderate-to-severe AD using a matching-adjusted indirect comparison (MAIC). Methods: Phase 3 clinical trials of difamilast and delgocitinib for treating AD were included. The trials had similar designs but differed in baseline population characteristics. Anchored MAIC was used to align the baseline characteristics and calculate clinical outcomes. The primary outcome was to determine severity stages of the proportion of patients with AD through Eczema Area and Severity Index (EASI), while the secondary outcome included comparing other clinical efficacy and safety of difamilast with delgocitinib. Results: A total of 340 patients were selected (170 each received difamilast and placebo) from the difamilast trial, with 158 (106 received delgocitinib; 52 received placebo) from the delgocitinib trial for the analysis. After matching patients from the difamilast trial with those from the delgocitinib trial, the effective sample sizes (ESS) reduced to 32.7–43.3% of the original difamilast (treatment/placebo) patients. At week 4, the ESS in the difamilast group demonstrated no statistically significant differences in the distribution of AD severity stages, as per EASI scores, compared with the delgocitinib group. In addition, no significant differences were found in modified EASI (mEASI) scores, mEASI 50 and 75 scores, and safety outcomes between the two treatments. Conclusions: The anchored MAIC analysis indicates that difamilast treatment, like delgocitinib, is a useful option for the treatment of patients with moderate-to-severe AD in Japan. [ABSTRACT FROM AUTHOR]

Abstract Background Atopic dermatitis (AD) is a chronic condition with an increasing incidence in Japan. Difamilast and delgocitinib are both new topical drugs for AD proven to be efficacious and safe in phases 2 and 3 clinical trials in Japan. However, there are no head-to-head trials comparing their efficacy and safety. The aim of this study was to determine the proportion of patients by severity and compare the clinical efficacy and safety of difamilast with delgocitinib among patients with moderate-to-severe AD using a matching-adjusted indirect comparison (MAIC). Methods Phase 3 clinical trials of difamilast and delgocitinib for treating AD were included. The trials had similar designs but differed in baseline population characteristics. Anchored MAIC was used to align the baseline characteristics and calculate clinical outcomes. The primary outcome was to determine severity stages of the proportion of patients with AD through Eczema Area and Severity Index (EASI), while the secondary outcome included comparing other clinical efficacy and safety of difamilast with delgocitinib. Results A total of 340 patients were selected (170 each received difamilast and placebo) from the difamilast trial, with 158 (106 received delgocitinib; 52 received placebo) from the delgocitinib trial for the analysis. After matching patients from the difamilast trial with those from the delgocitinib trial, the effective sample sizes (ESS) reduced to 32.7–43.3% of the original difamilast (treatment/placebo) patients. At week 4, the ESS in the difamilast group demonstrated no statistically significant differences in the distribution of AD severity stages, as per EASI scores, compared with the delgocitinib group. In addition, no significant differences were found in modified EASI (mEASI) scores, mEASI 50 and 75 scores, and safety outcomes between the two treatments. Conclusions The anchored MAIC analysis indicates that difamilast treatment, like delgocitinib, is a useful option for the treatment of patients with moderate-to-severe AD in Japan.

Emotional labor is a crucial yet often overlooked aspect of effective leadership. To address this, the current study adopts the Emotion as Social Information (EASI) model as a theoretical framework to investigate the influence of leaders' emotional labor and perceived appropriateness on employees' emotional labor. A two (leaders' emotional labor strategies: surface acting vs. deep acting) by two (perceived appropriateness: appropriate vs. inappropriate) between-subjects experiment was designed with a sample of 120 front-line service employees from hotels in Shanghai. The results showed that regardless of whether the perception of a leader's surface acting was deemed appropriate or not, employees tended to perform surface acting, while the impact of the perceived appropriateness regarding the leader's deep acting was different, wherein an appropriate display of deep acting by the leader significantly influenced employees to engage in deep acting themselves. The managerial implications and limitations of the findings are also discussed. [ABSTRACT FROM AUTHOR]

Eblasakimab, an interleukin (IL)-13 receptor α1 antagonist, blocks IL-4 and IL-13 signaling through the type 2 receptor. The safety and efficacy of eblasakimab was evaluated in adults with moderate-to-severe atopic dermatitis (AD). In this phase 1b randomized, double-blinded study, 52 patients with moderate-to-severe AD received weekly subcutaneous injections of eblasakimab 200, 400, or 600 mg, or placebo for 8 weeks. Primary outcome was the incidence of treatment-emergent adverse events. Secondary outcomes included percentage change in the Eczema Area and Severity Index from baseline; Eczema Area and Severity Index improvement of at least 50%, 75%, or 90% from baseline; and percentage change in the peak-pruritus numeric rating scale score from baseline. Treatment-emergent adverse events were reported in 47% placebo and 71% eblasakimab patients; most were considered mild or moderate and did not lead to study discontinuation. At week 8 eblasakimab 600 mg showed statistically significant improvement in mean percentage change in Eczema Area and Severity Index versus placebo (–65% vs –27%, P =.014). Other key secondary physician- and patient-reported end points were met. Longer studies are required to confirm eblasakimab safety and efficacy in AD patients. Treatment of adults with moderate-to-severe AD with eblasakimab was well-tolerated and associated with significant clinical improvements versus placebo. [ABSTRACT FROM AUTHOR]

Introduction: There are few long-term effectiveness and safety data for dupilumab in the treatment of atopic dermatitis (AD). The aim of this study was to evaluate efficacy and safety of dupilumab for up to three years after treatment initiation. Materials and Methods: We collected data from patients ≥ 12 years with severe AD who started dupilumab at the Dermatology Clinic of the Turin University Hospital between December 2018 and October 2022. Clinic and patient reported outcomes were evaluated from baseline, up to 3 years (T9), every 4 months. Results: A total of 418 patients were observed. A progressive decrease in the meanEASI was observed: from 23.64 at baseline to 2.31 at T9. Similar trends were observed in patients' reported outcomes. The achievement of EASI75 and EASI90 was observed in 75.58% of patients and 53.49%, respectively, at T1 (4 months), and in 92.55% and 80.85% at T9; DLQI 0/1 was achieved at T9 in 61.7%. Mean NRSpp ≤ 4 was achieved at T9 in 91.5% (86 out of 94 patients). The most common adverse event was conjunctivitis occurring in 13% of patients on average at each timepoint analyzed. Conclusions: Dupilumab proved to be effective and safe for the treatment of AD in clinical practice, up to 3 years. [ABSTRACT FROM AUTHOR]

Abstract Objectives Atopic dermatitis (AD) is aggravated by various factors, including perspiration and heat. Thus, it is recommended that AD patients wear breathable clothing to maintain disease remission. Japan has four seasons, so the ideal clothing for individuals with AD may differ throughout the year. The aim of this study was to evaluate the impact of wearing a newly developed performance fabric, named the Comfiknit Atopic Eczema® T‐shirt, which absorbs excess perspiration from the skin surface and retains moisture within the fabric. We evaluated the effects of the T‐shirts on the clinical characteristics of AD and compared the effects in summer and winter. Methods Ten adult outpatients with AD took part in an open‐label pilot study for 4 weeks during the summer and for 4 weeks during the winter. The Eczema Area and Severity Index (EASI), the Patient‐Oriented Eczema Measure (POEM), the itch Visual Analogue Scale (VAS), the stratum corneum water content (SCWC), skin pH, and skin bacterial cultures were evaluated. A Treatment Satisfaction Questionnaire for Medication‐9 (TSQM‐9) was filled out only after the intervention. Results The mean EASI, POEM, and itch VAS scores in both summer and winter fell after wearing the Comfiknit Atopic Eczema® T‐shirts, whereas the SCWC increased. There was no significant difference in the skin surface pH or bacterial cultures before and after the intervention. Conclusions Wearing Comfiknit Atopic Eczema® T‐shirts helped to prevent exacerbation of AD in summer and winter. Thus, wearing T‐shirts made from performance fabric may help to maintain skin homeostasis.

Abstract Introduction Assessing treatment response is key to determining treatment value in atopic dermatitis (AD). Currently, response is assessed using various clinician- or patient-reported measures and response criteria. This variation creates a mismatch of evidence across trials, hindering the ability of clinicians, regulators, and payers to compare the efficacy of treatments. This review identifies which measures and criteria are used to determine response in clinical trials and health technology assessments (HTAs). Moreover, it systematically reviews the psychometric performance of those measures and criteria to understand which perform best in capturing patient-relevant symptoms and treatment benefits. Methods A scoping review of clinical trials and HTAs in AD identified the following measures for inclusion: the Eczema Area and Severity Index (EASI), the Investigator’s Global Assessment (IGA), the Dermatology Life Quality Index (DLQI) and the Peak Pruritus Numerical Rating Scale (PP-NRS). A systematic search was performed in MEDLINE and Embase to identify studies testing the psychometric performance of these measures in adults or adolescents with AD. Results A lack of consistency in the assessment of response was observed across clinical trials and HTAs. Important gaps in psychometric evidence were identified. No content validations of the EASI and IGA in AD were found, while some quantitative studies suggested that these measures fail to capture itch, a core symptom. The PP-NRS and DLQI performed well. No studies compared the performance of different response criteria. Conclusion Content validation of the PP-NRS confirmed the importance of itch as a core symptom and treatment priority in AD; however, itch is not well covered in the EASI or IGA. Including the PP-NRS in clinical trials and HTAs will better capture patient-relevant benefit and response. Although various response criteria were used, no studies compared the performance of different criteria to inform which were most appropriate to compare treatments in clinical trials and HTAs.

Abstract Introduction The treatment landscape for moderate-to-severe atopic dermatitis (AD) continues to expand. This network meta-analysis (NMA) updates a previously conducted NMA to include data from the most recent phase 3 trials to assess the comparative efficacy of targeted systemic therapies without the addition of topical corticosteroids (TCS) and/or topical calcineurin inhibitors (TCI) in adults with moderate-to-severe AD. Methods Data from recent phase 3 monotherapy trials of lebrikizumab, ADvocate1 (NCT04146363) and ADvocate2 (NCT04178967), were included in the analyses, along with other eligible phase 3/4 randomized placebo-controlled trials for abrocitinib, baricitinib, dupilumab, tralokinumab, and upadacitinib identified through a systemic literature review in Silverberg et al. (Dermatol Ther (Heidelb) 12(5):1181–1196, 2022). The proportion of patients achieving Eczema Area and Severity Index (EASI) improvement ≥ 90% from baseline (EASI-90), EASI improvement ≥ 75% from baseline (EASI-75), ≥ 4-point improvement on Pruritus Numerical Rating Scale from baseline (ΔNRS ≥ 4), and Investigator Global Assessment (IGA) score of 0 or 1 (clear or almost clear) and reduction of ≥ 2 points from baseline (IGA 0/1) were evaluated using a Bayesian network meta-analysis. Results The updated NMA analyzed 13 unique placebo-controlled trials involving 7105 patients in 32 arms across 6 targeted therapies. Upadacitinib 30 mg was the most efficacious therapy across all endpoints at the primary timepoint (week 12 or 16) and at earlier timepoints, generally followed by abrocitinib 200 mg, upadacitinib 15 mg, dupilumab 300 mg, and lebrikizumab 250 mg or abrocitinib 100 mg. Baricitinib 2 mg and tralokinumab were generally ranked lower across outcomes. Conclusions Many factors need to be considered for treatment selection for AD, especially as new treatments continue to emerge. After incorporating recent placebo-controlled phase 3 data of lebrikizumab, upadacitinib 30 mg, upadacitinib 15 mg, and abrocitinib 200 mg remain the most efficacious targeted systemic therapies over 12–16 weeks of therapy in AD. These updated findings can help healthcare providers when creating a patient’s personalized treatment plan.

According to recent data, the key molecules in the pathogenesis of atopic dermatitis are the cytokines IL-4 and IL-13, which initiate and maintain Th2 inflammation. Targeted therapy with dupilumab inhibits the signaling function of these cytokines by binding to the IL-4Rα subunit, which is part of the IL-4 and IL-13 receptor complexes. The drug is approved for the treatment of patients over 6 years of age with moderate to severe AD. The efficacy and safety of dupilumab have been confirmed by the results of clinical studies. Materials and methods. 27 children with severe AD at the age of 8–18 years were under constant supervision. All patients received systemic treatment with dupilumab, topically used topical glucocorticosteroids (if necessary), emollients (twice a day). Dosing of dupilumab was carried out according to the instructions for the drug. Results. After 26 weeks of complex therapy, 96,3 % of patients achieved an IGA index value of 0/1 and an improvement of 75 % according to the EASI-75 index. The SCORAD index dropped from an average of 78,8 points to 13,7. The average value of total IgE after 6 months decreased by 1518 kU/l. In 2 (7,4 %) patients, conjunctivitis was noted, which was not a reason to discontinue the drug. Conclusion. During treatment with dupilumab, there is a significant decrease in the severity of the main symptoms of atopic dermatitis, including itching, exacerbations.

Background: To develop precision medicine for atopic dermatitis (AD), it is critical to establish relevant biomarkers. However, the characteristics of various biomarkers have not been fully understood. We previously carried out the Biomarkers to Predict Clinical Improvement of AD in Patients Treated with Dupilumab (B-PAD) study, a comprehensive nationwide study in Japan, to explore biomarkers for AD. Objective: The aim of this study is to find biomarkers associated with objective and subjective clinical findings in patients with moderate-to-severe AD based on the B-PAD study and to identify biomarkers sensitive enough to assess the severity of AD. Methods: We performed the B-PAD study as a consortium composed of 19 medical facilities in Japan, enrolling 110 patients with moderate-to-severe AD. We evaluated the Eczema Area and Severity Index (EASI) for objective assessment as well as the Patient-Oriented Eczema Measure (POEM) and a numeric rating scale for pruritus (pruritis-NRS) for subjective assessment, measuring 19 biomarkers at baseline. Results: We found that 12, 6, and 7 biomarkers showed significant and positive associations with the EASI, POEM, and pruritis-NRS, respectively. Most of the biomarkers associated with either the POEM or the pruritis-NRS were included among the biomarkers associated with EASI. Of the biomarkers examined, CCL26/eotaxin-3 and SCCA2 were the most capable of assessing severity for EASI, as shown by the 2 kinds of receiver operating characteristic analyses, respectively, whereas lactate dehydrogenase was the best for both the POEM and pruritis-NRS, again using the 2 analyses. Conclusion: We found biomarkers associated with the EASI, POEM, and pruritis-NRS, respectively, based on the B-PAD study. Moreover, we identified CCL26/eotaxin-3 and/or SCCA2 as the biomarkers having the greatest ability to assess severity in the EASI; lactate dehydrogenase did the same for the POEM and pruritis-NRS. These findings will be useful in treating patients with moderate-to-severe AD.

Introduction: Assessing treatment response is key to determining treatment value in atopic dermatitis (AD). Currently, response is assessed using various clinician- or patient-reported measures and response criteria. This variation creates a mismatch of evidence across trials, hindering the ability of clinicians, regulators, and payers to compare the efficacy of treatments. This review identifies which measures and criteria are used to determine response in clinical trials and health technology assessments (HTAs). Moreover, it systematically reviews the psychometric performance of those measures and criteria to understand which perform best in capturing patient-relevant symptoms and treatment benefits. Methods: A scoping review of clinical trials and HTAs in AD identified the following measures for inclusion: the Eczema Area and Severity Index (EASI), the Investigator's Global Assessment (IGA), the Dermatology Life Quality Index (DLQI) and the Peak Pruritus Numerical Rating Scale (PP-NRS). A systematic search was performed in MEDLINE and Embase to identify studies testing the psychometric performance of these measures in adults or adolescents with AD. Results: A lack of consistency in the assessment of response was observed across clinical trials and HTAs. Important gaps in psychometric evidence were identified. No content validations of the EASI and IGA in AD were found, while some quantitative studies suggested that these measures fail to capture itch, a core symptom. The PP-NRS and DLQI performed well. No studies compared the performance of different response criteria. Conclusion: Content validation of the PP-NRS confirmed the importance of itch as a core symptom and treatment priority in AD; however, itch is not well covered in the EASI or IGA. Including the PP-NRS in clinical trials and HTAs will better capture patient-relevant benefit and response. Although various response criteria were used, no studies compared the performance of different criteria to inform which were most appropriate to compare treatments in clinical trials and HTAs. Plain Language Summary: The assessment of treatment response is important in determining treatment value in atopic dermatitis (AD). This study aimed to identify which outcome measures and criteria are used to determine treatment response in clinical trials and health technology assessments (HTAs). The psychometric performance of identified outcome measures and criteria was then systematically reviewed to understand which perform best in capturing patient-relevant symptoms and treatment benefits in AD. The review identified and included the Eczema Area and Severity Index (EASI), Investigator's Global Assessment (IGA), Dermatology Life Quality Index (DLQI) and Peak Pruritus Numerical Rating Scale (PP-NRS) as response measures. Lack of consistency in how response is assessed across clinical trials and HTAs makes it difficult for clinicians and payers to compare the efficacies and cost-effectivenesses of different treatments and to make optimal treatment decisions. The review found that content validity (the extent to which a measure covers those symptoms and treatment benefits which are important to patients) was not assessed for EASI and IGA. EASI and IGA are often used to assess response in clinical trials and HTAs, but they miss key elements of the patient-relevant disease impact and treatment benefit, including itch. Treatments leading to improvements in missed symptoms (e.g. itch) will be undervalued using EASI and IGA, decreasing the chances of regulatory approval and reimbursement. Moreover, response criteria used in clinical trials and HTAs are sometimes adopted in prescriber settings. Here, if response assessment does not capture patient-relevant benefit, patients' access to tailored treatment may be restricted due to the perceived non-response. [ABSTRACT FROM AUTHOR]

His bundle pacing (HBP) has become popular in recent years as a more physiological alternative to conventional right ventricular pacing. Implantation requires 12‑lead ECG during surgery, which is not readily available in a standard operating room. Often but not always HBP is performed in an electrophysiology lab. EASI is a reduced lead system which enables derived 12‑lead ECG. EASI derived 12‑lead ECGs on modern tablet computers offer a more mobile and lightweight ECG solution which does not obstruct fluoroscopy during implantation. This case series aims to compare standard 12‑lead ECG to EASI derived 12‑lead ECG in patients undergoing HBP implantation. A total of 11 patients received permanent HBP guided only by fluoroscopy, a pacing system analyzer (Medtronic CareLink SmartSync Device Manager) and EASI derived 12‑lead ECG (CardioSecur Pro). During the first postoperative device interrogation HBP criteria, as defined in the EHRA consensus paper on conduction system pacing, were evaluated with the EASI derived system as well as a standard 12‑lead ECG and compared to each other. There was perfect agreement with regards to these criteria which lead to identical conclusions in all cases. HBP implantation can be performed with EASI derived 12‑lead ECG instead of conventional 12‑lead ECG. Criteria for discriminating between selective His bundle, non-selective His bundle or myocardial capture alone are clearly visible in the EASI derived ECG leading to the same conclusion when compared to standard 12‑lead ECG. Compared to a conventional 12‑lead ECG the EASI system offers a leaner setup with less visual obstruction on fluoroscopy. [ABSTRACT FROM AUTHOR]

Introduction: The treatment landscape for moderate-to-severe atopic dermatitis (AD) continues to expand. This network meta-analysis (NMA) updates a previously conducted NMA to include data from the most recent phase 3 trials to assess the comparative efficacy of targeted systemic therapies without the addition of topical corticosteroids (TCS) and/or topical calcineurin inhibitors (TCI) in adults with moderate-to-severe AD. Methods: Data from recent phase 3 monotherapy trials of lebrikizumab, ADvocate1 (NCT04146363) and ADvocate2 (NCT04178967), were included in the analyses, along with other eligible phase 3/4 randomized placebo-controlled trials for abrocitinib, baricitinib, dupilumab, tralokinumab, and upadacitinib identified through a systemic literature review in Silverberg et al. (Dermatol Ther (Heidelb) 12(5):1181–1196, 2022). The proportion of patients achieving Eczema Area and Severity Index (EASI) improvement ≥ 90% from baseline (EASI-90), EASI improvement ≥ 75% from baseline (EASI-75), ≥ 4-point improvement on Pruritus Numerical Rating Scale from baseline (ΔNRS ≥ 4), and Investigator Global Assessment (IGA) score of 0 or 1 (clear or almost clear) and reduction of ≥ 2 points from baseline (IGA 0/1) were evaluated using a Bayesian network meta-analysis. Results: The updated NMA analyzed 13 unique placebo-controlled trials involving 7105 patients in 32 arms across 6 targeted therapies. Upadacitinib 30 mg was the most efficacious therapy across all endpoints at the primary timepoint (week 12 or 16) and at earlier timepoints, generally followed by abrocitinib 200 mg, upadacitinib 15 mg, dupilumab 300 mg, and lebrikizumab 250 mg or abrocitinib 100 mg. Baricitinib 2 mg and tralokinumab were generally ranked lower across outcomes. Conclusions: Many factors need to be considered for treatment selection for AD, especially as new treatments continue to emerge. After incorporating recent placebo-controlled phase 3 data of lebrikizumab, upadacitinib 30 mg, upadacitinib 15 mg, and abrocitinib 200 mg remain the most efficacious targeted systemic therapies over 12–16 weeks of therapy in AD. These updated findings can help healthcare providers when creating a patient's personalized treatment plan. [ABSTRACT FROM AUTHOR]

Objectives: Atopic dermatitis (AD) is aggravated by various factors, including perspiration and heat. Thus, it is recommended that AD patients wear breathable clothing to maintain disease remission. Japan has four seasons, so the ideal clothing for individuals with AD may differ throughout the year. The aim of this study was to evaluate the impact of wearing a newly developed performance fabric, named the Comfiknit Atopic Eczema® T‐shirt, which absorbs excess perspiration from the skin surface and retains moisture within the fabric. We evaluated the effects of the T‐shirts on the clinical characteristics of AD and compared the effects in summer and winter. Methods: Ten adult outpatients with AD took part in an open‐label pilot study for 4 weeks during the summer and for 4 weeks during the winter. The Eczema Area and Severity Index (EASI), the Patient‐Oriented Eczema Measure (POEM), the itch Visual Analogue Scale (VAS), the stratum corneum water content (SCWC), skin pH, and skin bacterial cultures were evaluated. A Treatment Satisfaction Questionnaire for Medication‐9 (TSQM‐9) was filled out only after the intervention. Results: The mean EASI, POEM, and itch VAS scores in both summer and winter fell after wearing the Comfiknit Atopic Eczema® T‐shirts, whereas the SCWC increased. There was no significant difference in the skin surface pH or bacterial cultures before and after the intervention. Conclusions: Wearing Comfiknit Atopic Eczema® T‐shirts helped to prevent exacerbation of AD in summer and winter. Thus, wearing T‐shirts made from performance fabric may help to maintain skin homeostasis. [ABSTRACT FROM AUTHOR]

Emotional labor is a crucial yet often overlooked aspect of effective leadership. To address this, the current study adopts the Emotion as Social Information (EASI) model as a theoretical framework to investigate the influence of leaders’ emotional labor and perceived appropriateness on employees’ emotional labor. A two (leaders’ emotional labor strategies: surface acting vs. deep acting) by two (perceived appropriateness: appropriate vs. inappropriate) between-subjects experiment was designed with a sample of 120 front-line service employees from hotels in Shanghai. The results showed that regardless of whether the perception of a leader’s surface acting was deemed appropriate or not, employees tended to perform surface acting, while the impact of the perceived appropriateness regarding the leader’s deep acting was different, wherein an appropriate display of deep acting by the leader significantly influenced employees to engage in deep acting themselves. The managerial implications and limitations of the findings are also discussed.

The Physical Protection System (PPS) plays an important role and must effectively deal with various adversary attacks in nuclear security. In specific single adversary path scenarios, we can calculate the PPS effectiveness by EASI (Estimated Adversary Sequence Interruption) through Probability of Interruption (PI) calculation. EASI uses a single value of the probability of detection (PD) and the probability of alarm communications (PC) in the PPS. In this study, we develop a multi-path analysis code based on EASI to evaluate the effectiveness of PPS. Our quantification method for PI considers the variability and uncertainty of PD and PC value by Monte Carlo simulation. We converted the 2-D scheme of the nuclear facility into an Adversary Sequence Diagram (ASD). We used ASD to find the adversary path with the lowest probability of interruption as the most vulnerable paths (MVP). We examined a hypothetical facility (Hypothetical National Nuclear Research Facility - HNNRF) to confirm our code compared with EASI. The results show that implementing the variability extension can estimate the PI value and its associated uncertainty. The multi-path analysis code allows the analyst to make it easier to assess PPS with more extensive facilities with more complex adversary paths. However, the variability of the PD value in each protection element allows a significant decrease in the PI value. The possibility of this decrease needs to be an important concern for PPS designers to determine the PD value correctly or set a higher standard for PPS performance that remains reliable.

TREATgermany is an investigator-initiated prospective disease registry. It investigates physician- and patient-reported disease severity (Eczema Area and Severity Index (EASI), objective Scoring Atopic Dermatitis (oSCORAD), Investigator Global Assessment, Patient-Oriented Eczema Measure (POEM), Patient Global Assessment (PGA)), patient-reported symptoms (itch, sleep loss, depressive symptoms), therapy courses and dermatological quality of life (DLQI) in moderate-to-severe atopic dermatitis with SCORAD >20. 1,134 atopic dermatitis patients (mean age 41.0±14.7 years, 42.5% females) were enrolled by 40 German recruiting sites (dermatological clinics and practices) between June 2016 and April 2021. The current analysis focuses on itch scores obtained with a numerical rating scale (NRS)) documented for the previous 3 days prior to baseline visit. The results show that 97.2% (1,090 of 1,121) patients experienced itch. Itch severity correlated moderately with severity of atopic dermatitis oSCORAD (rho=0.44 (0.39–0.48)) and EASI score (rho=0.41 (0.36–0.46)). A strong correlation was found with self-reported disease severity as PGA (rho=0.68 (0.65–0.71)), POEM sum score (rho=0.66 (0.63–0.69)) and dermatological quality of life impairment DLQI (rho=0.61 (0.57–0.65)). Itch as a subjective complaint is more closely correlated with patient-reported outcomes than with objective assessments by the physician. [ABSTRACT FROM AUTHOR]

Introduction: There are few long-term effectiveness and safety data for dupilumab in the treatment of atopic dermatitis (AD). The aim of this study was to evaluate efficacy and safety of dupilumab for up to three years after treatment initiation. Materials and Methods: We collected data from patients ≥ 12 years with severe AD who started dupilumab at the Dermatology Clinic of the Turin University Hospital between December 2018 and October 2022. Clinic and patient reported outcomes were evaluated from baseline, up to 3 years (T9), every 4 months. Results: A total of 418 patients were observed. A progressive decrease in the meanEASI was observed: from 23.64 at baseline to 2.31 at T9. Similar trends were observed in patients’ reported outcomes. The achievement of EASI75 and EASI90 was observed in 75.58% of patients and 53.49%, respectively, at T1 (4 months), and in 92.55% and 80.85% at T9; DLQI 0/1 was achieved at T9 in 61.7%. Mean NRSpp ≤ 4 was achieved at T9 in 91.5% (86 out of 94 patients). The most common adverse event was conjunctivitis occurring in 13% of patients on average at each timepoint analyzed. Conclusions: Dupilumab proved to be effective and safe for the treatment of AD in clinical practice, up to 3 years.

TREATgermany is an investigator-initiated prospective disease registry. It investigates physician- and patient-reported disease severity (Eczema Area and Severity Index (EASI), objective Scoring Atopic Dermatitis (oSCORAD), Investigator Global Assessment, Patient-Oriented Eczema Measure (POEM), Patient Global Assessment (PGA)), patient-reported symptoms (itch, sleep loss, depressive symptoms), therapy courses and dermatological quality of life (DLQI) in moderate-to-severe atopic dermatitis with SCORAD > 20. 1,134 atopic dermatitis patients (mean age 41.0 ± 14.7 years, 42.5% females) were enrolled by 40 German recruiting sites (dermatological clinics and practices) between June 2016 and April 2021. The current analysis focuses on itch scores obtained with a numerical rating scale (NRS)) documented for the previous 3 days prior to baseline visit. The results show that 97.2% (1,090 of 1,121) patients experienced itch. Itch severity correlated moderately with severity of atopic dermatitis oSCORAD (rho = 0.44 (0.39–0.48)) and EASI score (rho = 0.41 (0.36–0.46)). A strong correlation was found with self-reported disease severity as PGA (rho = 0.68 (0.65–0.71)), POEM sum score (rho = 0.66 (0.63–0.69)) and dermatological quality of life impairment DLQI (rho = 0.61 (0.57–0.65)). Itch as a subjective complaint is more closely correlated with patient-reported outcomes than with objective assessments by the physician.

The purpose of this trial was to compare extra-amniotic saline infusion (EASI) and intravaginal isoniazid (INH) for cervical ripening. This randomised clinical trial included 150 pregnant women who were undergoing induction of labour and who required pre-induction cervical ripening. Patients were randomly assigned to receive EASI or intravaginal INH. Bishop's score at the beginning of the study and before oxytocin infusion was not significantly different between INH and EASI groups. However, the time from first intervention to the beginning of the induction and also to the beginning of the active phase were significantly shorter in EASI group (p value ≤.001). Moreover, INH did not influence the labour process after the beginning of the active phase of labour. In conclusion, INH could be used for cervical ripening especially in the outpatient setting; however, it is a slower ripening agent compared to EASI. What is already known on this subject? To date there has been only one study about the safety and effectiveness of isoniazid (INH) in cervical ripening at term pregnancy which has compared INH with misoprostol. What do the results of this study add? The results of this study showed that vaginal INH is an effective agent for cervical ripening at term but in comparison to extra-amniotic saline infusion (EASI) it takes a longer time. What are the implications of these findings for clinical practice and/or further research? INH can be used in outpatient settings for cervical ripening at term pregnancy which makes it convenient for patient and cost effective for both patient and health system. Further studies are needed to discover the clinical efficacy of INH in comparison to other ripening methods and also the best dosage of INH for cervical ripening. [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis (AD) is one of the most prevalent skin diseases, but there are numerous knowledge gaps surrounding the impact this disease has on quality of life (QoL), mental health, and out-of-pocket expenses involved in the management of AD. The available scientific evidence on the multidimensional burden of AD is usually based on studies with measures reported by patients themselves., Methods: In this context, the MEASURE-AD trial was developed as a cross-sectional, multicenter, multinational trial using patient- and physician-reported measures to characterize the multidimensional burden of AD in adults with moderate-to-severe AD., Results: This paper presents the results of the Spanish cohort. We found that Spanish adults with moderate-to-severe AD and high EASI score (21.1-72) had a significantly increased disease burden, high severity of symptoms such as itch and sleep disturbances, impaired mental health and QoL, higher use of health care resources, and more out-of-pocket expenses than patients with low EASI scores (0-7 or 7.1-21)., Conclusions: This study provides information to better understand disease burden, and identify aspects to be improved in the management of AD., (Copyright © 2024 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction: Atopic dermatitis (AD) is a genetically based chronic inflammatory dermatosis associated with multiple triggers and complex pathophysiological mechanisms. Nowadays, an authentic therapeutic revolution is taking place with the incorporation of biological drugs for the treatment of moderate and severe atopic dermatitis. A new systematic revision (RS) is necessary to support decision-making for specialists treating AD. Methods: A literature search of MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials was performed between 1 January 2000 and 30 April 2022. Phase III randomized clinical trials (RCTs) of EMA-approved molecules were included. The main variables analyzed were a 75% improvement in the Eczema Area and Severity Index (EASI 75) and the number of patients who reached 0 in the Investigator Global Assessment (IGA) (fully cleared patients) or IGA 1 (almost cleared patients) at the end of the study period (week 48–60). The risk of bias was analyzed with the Cochrane Risk of Bias Assessment (ROB-2) tool, focused on the primary objectives. Before carrying out the study, the protocol was registered in PROSPERO with the number CRD42022331109. Results: A total of 3299 studies were systematically identified via databases and registers (442 from PubMed/MEDLINE, 2857 from Embase and 719 from CENTRAL). Finally, five publications containing seven RCTs were included in the final sample of detailed data extraction and data analyses. Regarding efficacy, the best results are obtained with Upadacitinib 30 mg (84.7% (77.3–92.1)) at 52 weeks, slightly improving its results when TCS is added (84.9% (80.3–89.5)). These results are replicated in the measurement of vIGA 0/1 for Updacitinib 30 mg + TCS, where 65.5% (55.7–75.2) of patients maintain it at 52 weeks. Of the four drugs, no long-term safety results have been reported for baricitinib. In relation to the safety findings, there were no significant differences in the dropout rates for this reason in the remaining three drugs. Discussion: Today, different therapeutic options for AD patients can be prescribed. Individualizing the treatment allows for better therapeutic consistency, in addition to being cost-efficient to avoid primary therapeutic failures. The results of the present SR may provide us with a useful basis for the preparation of management guidelines for the use of new generation therapies in moderate to severe atopic dermatitis. [ABSTRACT FROM AUTHOR]

Employee silence has multiple negative effects on the organization. Studies on the influence of leader negative emotional expression on employee silence are extremely limited, and there are inconsistent findings for the expression of negative emotion among leaders, which highlight the need to explore boundary factors in this field. The purpose of this paper is based on EASI model to examine the impact of leaders' negative emotional expression on employee silence through the perceptions of psychological safety. Moreover, drawing on social exchange theory, this paper proposed a moderated mediation model to explore how leader–member exchange (LMX) moderates the indirect relationship between leader negative emotional expression and employee silence through perceptions of psychological safety. We employed a bootstrapping technique to analyze the hypotheses. This study adopts two-wave surveys and the results shown that leader negative emotional expression triggered employee silence by employees' perceptions of psychological safety. This study also demonstrated that LMX weakens the relationship between leader negative emotional expression and employees' perceptions of psychological safety. Furthermore, LMX weakens the indirect relationship between leader negative emotional expression and employee silence through employees' perceptions of psychological safety. Using multiphase data collection, we found that when LMX is at a low level, the indirect effect of leader negative emotional expression on employee silence through employee psychological safety is stronger. The theoretical, practical implications and future research suggestions are discussed. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a common inflammatorydermatosis characterized by pruritus, erythema,induration, and lichenification. Current treatmentoptions for generalized atopic dermatitis arelimited and have potentially serious adverse effects,especially in patients with severe, chronic AD whofrequently require systemic anti-inflammatory agents.Apremilast, an oral phosphodiesterase-4 inhibitor, wasFDA approved in September 2014 for the treatmentof moderate-to-severe plaque psoriasis. However, itsupstream anti-inflammatory effects, ease of use asan oral agent, and mild side-effect profile make it aninteresting treatment option for AD as well. Herein,we present a patient with a life-long history of ADrecalcitrant to topical steroids and cyclosporine whoattained subjective and objective improvement inpruritus and erythema after 10-week treatment withapremilast.

Employee silence has multiple negative effects on the organization. Studies on the influence of leader negative emotional expression on employee silence are extremely limited, and there are inconsistent findings for the expression of negative emotion among leaders, which highlight the need to explore boundary factors in this field. The purpose of this paper is based on EASI model to examine the impact of leaders’ negative emotional expression on employee silence through the perceptions of psychological safety. Moreover, drawing on social exchange theory, this paper proposed a moderated mediation model to explore how leader–member exchange (LMX) moderates the indirect relationship between leader negative emotional expression and employee silence through perceptions of psychological safety. We employed a bootstrapping technique to analyze the hypotheses. This study adopts two-wave surveys and the results shown that leader negative emotional expression triggered employee silence by employees’ perceptions of psychological safety. This study also demonstrated that LMX weakens the relationship between leader negative emotional expression and employees’ perceptions of psychological safety. Furthermore, LMX weakens the indirect relationship between leader negative emotional expression and employee silence through employees’ perceptions of psychological safety. Using multiphase data collection, we found that when LMX is at a low level, the indirect effect of leader negative emotional expression on employee silence through employee psychological safety is stronger. The theoretical, practical implications and future research suggestions are discussed.

Introduction: The comparative efficacy of targeted systemic therapies for moderate to severe atopic dermatitis (AD) has not been systematically assessed using recent phase 3 data. This network meta-analysis assesses the comparative efficacy of targeted systemic therapies without the addition of topical corticosteroids (TCS) and/or topical calcineurin inhibitors (TCI) in adults with moderate to severe AD. Methods: The systematic literature review searched through 17 May 2021 for phase 3/4 trials with upadacitinib, interleukin-4 (IL-4), interleukin-13 (IL-13), or JAK inhibitors compared with placebo or active intervention for adults and adolescents with moderate to severe AD with inadequate response to TCS/TCI or for whom TCS/TCI was medically inadvisable, without restrictions on year or region. Researchers assessed data using PRISMA guidelines. The proportion of patients achieving trial co-primary endpoints [Investigator Global Assessment (IGA) score of 0 or 1 (clear or almost clear) and reduction of ≥ 2 points from baseline; proportion of patients achieving Eczema Area and Severity Index (EASI) improvement ≥ 75% from baseline (EASI-75)]; EASI improvement ≥ 90% from baseline (EASI-90); and ≥ 4-point improvement on Pruritus Numerical Rating Scale from baseline (ΔNRS ≥ 4) were evaluated using Bayesian network meta-analysis. Results: Of 3415 initially identified records, network meta-analysis (NMA) ultimately included 6 records representing 9 unique studies. Two upadacitinib trials were also included. Eleven clinical trials including 6254 patients were analyzed. Upadacitinib 30 mg daily was the most efficacious therapy across all endpoints at the primary endpoint (week 12 or 16) and at earlier timepoints, followed by upadacitinib 15 mg daily and abrocitinib 200 mg daily. Discussion: Many factors need to be considered for treatment selection for AD. These findings can help healthcare providers when personalizing a patient's treatment. Conclusion: Upadacitinib 30 mg daily, upadacitinib 15 mg daily, and abrocitinib 200 mg daily may be the most efficacious targeted systemic therapies over 12–16 weeks of therapy in AD. [ABSTRACT FROM AUTHOR]

Introduction: Atopic dermatitis (AD) can affect multiple body regions and is especially burdensome when involving exposed skin areas. Rapid, effective treatment of AD across body regions remains an unmet need, particularly for difficult-to-treat areas such as the head and neck area. We investigated the temporal and regional patterns of clinical improvement in AD with the use of abrocitinib, an orally available Janus kinase 1 selective inhibitor under development for the treatment of moderate-to-severe AD. Methods: We performed a post hoc analysis of data from JADE COMPARE, a phase 3, multicenter, randomized, double-blind, double-dummy trial that evaluated the efficacy and safety of abrocitinib 200 mg once daily, abrocitinib 100 mg once daily, dupilumab 300 mg subcutaneous injection every 2 weeks, and placebo in adult patients with moderate-to-severe AD who were concomitantly receiving medicated topical therapy. Assessments included the Eczema Area and Severity Index (EASI) and SCORing Atopic Dermatitis (SCORAD) index. Results: With abrocitinib 200 mg, time to ≥ 75% improvement in EASI (EASI-75) occurred at a median of 29 days across body regions, including the head and neck region. With abrocitinib 100 mg, EASI-75 response was achieved at a median of 30–32 days for the trunk and lower limbs, and at 56–57 days for the head and neck region and upper limbs. With dupilumab, EASI-75 response was achieved at a median of 43 days for the trunk and 57 days for other regions. EASI body region scores significantly improved with abrocitinib 200 mg and 100 mg versus placebo at week 2 (p < 0.0001 for all comparisons). Improvements with abrocitinib were maintained up to week 16. Conclusions: Rapid and persistent improvement in AD across all body regions was observed with abrocitinib treatment. Abrocitinib may be useful in patients with AD that affects difficult-to-treat anatomical areas or who require a rapid response. Trial registration: Clinicaltrials.gov identifier: NCT03720470. Plain Language Summary: Atopic dermatitis (AD) is the most common form of eczema. It is a long-lasting skin disease that often affects multiple body regions. AD may decrease a person's quality of life, especially when it involves skin areas that are visible to others. Quick, effective treatment for AD across multiple body regions is needed, especially in areas that are difficult to treat and/or cosmetically important, such as the head and neck area. Abrocitinib is a medicine taken orally that is being developed to treat moderate-to-severe AD. Researchers analyzed data from a clinical study called JADE COMPARE (Clinicaltrials.gov identifier: NCT03720470). It evaluated the effectiveness and safety of abrocitinib 200 mg taken once daily, abrocitinib 100 mg taken once daily, and placebo (no study medication) plus medicated skin cream in adults with moderate-to-severe AD. Abrocitinib 200 mg and 100 mg significantly improved the extent and severity of AD as assessed by a measure called the Eczema Area and Severity Index (EASI) compared to placebo at week 2. Improvements were maintained for up to 16 weeks. With abrocitinib 200 mg, the time to ≥ 75% improvement in EASI (EASI-75) was approximately 29 days across body regions, including the head and neck region. With abrocitinib 100 mg, this EASI-75 response occurred at approximately 30 to 32 days for the trunk and legs and at 56 to 57 days for the head and neck region and arms. Abrocitinib may be effective in people with AD that affects difficult-to-treat parts of the body or in those who need a fast response. [ABSTRACT FROM AUTHOR]

Background: The use of photographs to diagnose and monitor skin diseases is gaining ground. Objectives: To investigate the validity and reliability of photographic assessments of atopic dermatitis (AD) severity. Methods: AD severity was evaluated in the clinic by two assessors using the Eczema Area and Severity Index (EASI), SCOring Atopic Dermatitis (SCORAD), and Investigator's Global Assessment (IGA). Participants photographed the lesions with their own smartphone and completed a questionnaire about the extent of eczema the same day from home. The photographs were assessed twice with an 8 weeks interval by five dermatologists experienced in photographic evaluations. Intraclass correlation coefficients (ICC) with 95% confidence interval (CI) were applied. Results: Seventy‐nine participants were enrolled. The ICC between clinical EASI and photographic EASI was 0.88 (95% CI 0.81–0.93), and 0.86 (0.70–0.93) between clinical SCORAD and photographic SCORAD. Perfect agreement between clinical IGA and photograph IGA was observed for 62%, with the difference between the two never deviating with more than 1 score. The inter‐rater ICC for photographic EASI and photographic SCORAD, respectively, was 0.90 (0.85–0.94), and 0.96 (0.91–0.98). The intra‐rater agreements between the first and second assessments varied from 0.95 to 0.98 for photographic EASI, and from 0.86 to 0.94 for photographic SCORAD. Conclusion: There was high agreement between mild to moderate AD severity assessed clinically and based on smartphone photographs. Further, the photographic assessments can be reproduced with high reliability. [ABSTRACT FROM AUTHOR]

Introduction: In a 52-week, phase 3 clinical trial (LIBERTY AD CHRONOS) in adult patients with moderate-to-severe atopic dermatitis (AD), dupilumab in combination with topical corticosteroids (TCS) resulted in a significant improvement in overall Eczema Area and Severity Index (EASI) compared with placebo plus TCS. In a post hoc analysis, dupilumab significantly improved the overall extent and severity of AD across four anatomic regions (head and neck, trunk, upper extremities, lower extremities) over 16 weeks. However, as AD severity and presentation may vary by body region, this analysis sought to determine whether there are regional variations in dupilumab efficacy. Methods: Using data from the LIBERTY AD CHRONOS study, we performed a post hoc analysis of the mean percentage change in individual EASI signs (erythema, infiltration/papulation, excoriation, lichenification) from baseline through week 52 across four anatomic regions (head and neck, trunk, upper extremities, lower extremities). Results: Dupilumab plus TCS, compared with placebo plus TCS, significantly improved the severity of all individual AD signs to a similar extent across the four anatomic regions. Significant improvements in each sign were seen early, within the first 2–4 weeks of treatment, and were sustained through week 52 across all regions. Conclusions: In adult patients with moderate-to-severe AD, treatment with dupilumab resulted in rapid and sustained improvement in the signs of AD across all anatomic regions. Trial registration: LIBERTY AD CHRONOS (NCT02260986). [ABSTRACT FROM AUTHOR]

Introduction/Background Atopic dermatitis (AD) is a chronic, recurrent, inflammatory disease characterized by multiple skin manifestations and intense itching that can impact patient quality of life. The effect of upadacitinib (UPA) and dupilumab (DUP) was evaluated in a double-blind, double-dummy, head-to-head phase 3b clinical trial (Heads Up; NCT03738397) of adult patients (age: 18-75 years) with moderate-to-severe AD (Eczema Area and Severity Index [EASI] =16; body surface area =10%; validated Investigator Global Assessment of Atopic Dermatitis (vIGA-AD) =3 at screening and baseline; Worst Pruritus Numerical Rating Scale [WP-NRS] =4 at baseline) randomized 1:1 to UPA 30 mg orally once-daily (N=348) or DUP 300 mg subcutaneous injection every two weeks after a 600 mg loading dose (N=344). Objective The effects of UPA and DUP on skin clearance and itch improvement are reported here. Methods: Skin clearance was assessed by EASI, with response defined as an improvement =75% (EASI75), =90% (EASI90), and 100% (EASI100) from baseline. Itch intensity was assessed daily by WP-NRS up to week 16, then at study visits up to week 24. Weekly WP-NRS scores were analyzed as a 7-day rolling average up to week 16, then at study visits through week 24. Daily WP-NRS scores were analyzed day-to-day through day 28. Mean percent improvement and the proportion of patients achieving clinically meaningful improvement (=4-point improvement from baseline) were evaluated. The proportion of patients achieving a state of no/minimal itch (defined as WP-NRS score of 0/1) was evaluated as a posthoc analysis. Results: EASI75/90/100 response rates were significantly greater with UPA versus DUP at week 16 (UPA = 72.4%/61.6%/28.4%, DUP = 62.6%/40.3%/7.9%; P<0.01 for all comparisons), with greater EASI75 and EASI90 rates observed with UPA as early as week 1 (nominal P<0.05). Mean percent improvement in weekly WP-NRS was significantly greater with UPA versus DUP at week 16 (UPA = 67.8%, DUP= 49.6%; P<0.001), with greater improvement observed as early as week 1 (nominal P<0.001). Daily WP-NRS data showed a greater mean percent improvement with UPA versus DUP as early as day 2, the day after the first dose (UPA = 22.0%, DUP = 4.2%; nominal P<0.001). The proportion of patients that achieved clinically meaningful improvement in weekly WP-NRS was significantly greater with UPA versus DUP at week 16 (UPA = 56.1%, DUP = 36.4%; P<0.001), with greater proportions observed as early as week 1 (nominal P<0.001). Daily WP-NRS data showed a greater proportion of patients achieved clinically meaningful improvement with UPA versus DUP as early as day 2 (UPA = 15.3%, DUP = 3.4%; nominal P<0.001). The proportion of patients that achieved a state of no/minimal itch based on weekly WP-NRS was greater with UPA versus DUP at week 16 (UPA = 35.5%, DUP = 16.2%; nominal P<0.001) and at week 1 (nominal P<0.001). Conclusions: Skin clearance and itch improvement were consistently better with UPA compared with DUP in adult patients with moderate-to-severe AD, with greater improvements observed as early as week 1 for skin clearance and the day following treatment for itch improvement. [ABSTRACT FROM AUTHOR]

Introduction/Background Atopic dermatitis (AD) is a debilitating chronic inflammatory skin disease with fluctuating disease severity that requires long-term control. Patients report that complete or almost complete skin clearance is highly important as a treatment goal. Upadacitinib is a selective oral Janus kinase (JAK) inhibitor with greater inhibitory potency for JAK1 vs JAK2, JAK3, and tyrosine kinase 2. Objectives: In this post-hoc analysis of the upadacitinib phase 3/3b studies, we analyzed the time patients spent in skin clearance response states over 16 weeks with upadacitinib 15 mg (UPA 15) and 30 mg (UPA 30) compared to placebo and dupilumab. Methods: Data were from phase 3/3b multicenter, randomized, double-blinded studies comparing the safety and efficacy of upadacitinib to either placebo (Measure Up 1 and Measure Up 2) or dupilumab (Heads Up) in patients with moderate-to-severe AD. In the Measure Up 1 and Measure Up 2 studies, adults and adolescents were randomized to receive UPA 15, UPA 30, or placebo once daily for 16 weeks. In the Heads Up study, adults were randomized to receive UPA 30 once daily or dupilumab 300 mg every 2 weeks beginning at week 2 following an initial loading dose of 600 mg. The days patients spent in skin clearance response states based on Eczema Area Severity Index (EASI) improvements =75%/90%/100% (EASI 75/90/100) from baseline were assessed. Missing data at study visits were imputed using non-responder imputation. Response states between study visits were interpolated using last observation carried forward. Results: Integrated data from Measure Up 1 and Measure Up 2 included 1683 adults and adolescents randomized to UPA 15 (N=557), UPA 30 (N=567), or placebo (N=559); 44.0% were female, and 48.8% had previously received systemic therapy. In the Heads Up study, 673 adults were randomized to UPA 30 (N=342) or dupilumab (N=331); 44.3% were female, and 52.7% had previously received systemic therapy. Patients in Measure Up 1 and 2 taking UPA 15 or UPA 30 cumulatively spent a greater proportion of days in EASI 75 (UPA 15: 54.2%, UPA 30: 64.6%, Placebo: 10.2%), EASI 90 (UPA 15: 32.0%, UPA 30: 44.0%, Placebo: 3.2%), and EASI 100 (UPA 15: 7.5%, UPA 30: 13.5%, Placebo: 0.6%) response states compared to placebo over 16 weeks. In the Heads Up study, patients taking UPA 30 vs dupilumab cumulatively spent a greater proportion of days in EASI 75 (67.1% vs 44.9%), EASI 90 (47.0% vs 23.2%), and EASI 100 (12.6% vs 3.6%) response states over 16 weeks. Conclusions: Treatment of moderate-to-severe AD with UPA 15 or UPA 30 resulted in a greater proportion of days spent with higher levels of skin clearance (EASI 75/90/100) compared to placebo over 16 weeks, mirroring findings from the Heads Up study comparing UPA 30 to dupilumab. Increases in time spent with high levels of skin clearance with upadacitinib treatment may reflect improved long-term disease control and translate into more time spent experiencing a better quality of life that is less burdened by AD. [ABSTRACT FROM AUTHOR]

Background: Baricitinib, an oral selective Janus kinase 1/Janus kinase 2 inhibitor, is being studied for moderate-to-severe atopic dermatitis (AD) in adults.Objective: To evaluate the efficacy and safety of baricitinib monotherapy in a North American phase 3 trial (BREEZE-AD5/NCT03435081) of adults with moderate-to-severe AD who responded inadequately or were intolerant to topical therapy.Methods: Patients (N = 440) were randomized 1:1:1 to once-daily placebo or baricitinib (1 mg or 2 mg). The primary endpoint was the proportion of patients achieving ≥75% reduction in the Eczema Area and Severity Index at week 16. A key secondary endpoint was the proportion of patients achieving a validated Investigator Global Assessment for AD score of 0 (clear)/1(almost clear) with ≥2-point improvement.Results: At week 16, the proportion of patients achieving Eczema Area and Severity Index was 8%, 13%, and 30% (P < .001, 2 mg vs placebo) and those with a validated Investigator Global Assessment for AD score of 0/1 were 5%, 13%, and 24% (P < .001, 2 mg vs placebo) for placebo, baricitinib 1 mg, and baricitinib 2 mg, respectively. Safety findings were similar to those of other baricitinib AD studies.Limitations: Short-term clinical trial results may not be generalizable to real-world settings.Conclusion: Baricitinib was efficacious for patients with moderate-to-severe AD with no new safety findings over 16 weeks. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic, pruritic, inflammatory dermatosis that affects up to 25% of children and 2% to 3% of adults. This guideline addresses important clinical questions that arise in the management and care of AD, providing updated and expanded recommendations based on the available evidence. In this first of 4 sections, methods for the diagnosis and monitoring of disease, outcomes measures for assessment, and common clinical associations that affect patients with AD are discussed. Known risk factors for the development of disease are also reviewed.

Introduction: Atopic dermatitis (AD) is a genetically based chronic inflammatory dermatosis associated with multiple triggers and complex pathophysiological mechanisms. Nowadays, an authentic therapeutic revolution is taking place with the incorporation of biological drugs for the treatment of moderate and severe atopic dermatitis. A new systematic revision (RS) is necessary to support decision-making for specialists treating AD. Methods: A literature search of MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials was performed between 1 January 2000 and 30 April 2022. Phase III randomized clinical trials (RCTs) of EMA-approved molecules were included. The main variables analyzed were a 75% improvement in the Eczema Area and Severity Index (EASI 75) and the number of patients who reached 0 in the Investigator Global Assessment (IGA) (fully cleared patients) or IGA 1 (almost cleared patients) at the end of the study period (week 48–60). The risk of bias was analyzed with the Cochrane Risk of Bias Assessment (ROB-2) tool, focused on the primary objectives. Before carrying out the study, the protocol was registered in PROSPERO with the number CRD42022331109. Results: A total of 3299 studies were systematically identified via databases and registers (442 from PubMed/MEDLINE, 2857 from Embase and 719 from CENTRAL). Finally, five publications containing seven RCTs were included in the final sample of detailed data extraction and data analyses. Regarding efficacy, the best results are obtained with Upadacitinib 30 mg (84.7% (77.3–92.1)) at 52 weeks, slightly improving its results when TCS is added (84.9% (80.3–89.5)). These results are replicated in the measurement of vIGA 0/1 for Updacitinib 30 mg + TCS, where 65.5% (55.7–75.2) of patients maintain it at 52 weeks. Of the four drugs, no long-term safety results have been reported for baricitinib. In relation to the safety findings, there were no significant differences in the dropout rates for this reason in the remaining three drugs. Discussion: Today, different therapeutic options for AD patients can be prescribed. Individualizing the treatment allows for better therapeutic consistency, in addition to being cost-efficient to avoid primary therapeutic failures. The results of the present SR may provide us with a useful basis for the preparation of management guidelines for the use of new generation therapies in moderate to severe atopic dermatitis.

This systematic review evaluates the efficacy, safety and economic impact of dupilumab compared to standard of care for uncontrolled moderate‐to‐severe atopic dermatitis (AD). Pubmed, EMBASE and Cochrane Library were searched for RCTs and health economic evaluations. Critical and important AD‐related outcomes were considered. The risk of bias and the certainty of the evidence were assessed using GRADE. Seven RCTs including 1845 subjects >12 years treated with dupilumab 16 to 52 weeks were evaluated. For adults, there is high certainty that dupilumab decreases SCORAD (MD −30,72; 95% CI −34,65% to −26,79%) and EASI‐75 (RR 3.09; 95% CI 2.45 to 3.89), pruritus (RR 2.96; 95% CI 2.37 to 3.70), rescue medication (RR 3.46; 95% CI 2.79 to 4.30), sleep disturbance (MD −7.29; 95% CI −8.23 to −6.35) and anxiety/depression (MD −3.08; 95% CI −4.41 to −1.75) and improves quality of life (MD −4.80; 95% CI −5.55 to −4.06). The efficacy for adolescents is similar. Dupilumab‐related adverse events (AEs) slightly increase (low certainty). The evidence for dupilumab‐related serious AE is uncertain. The incremental cost‐effectiveness ratio ranged from 28 500 £ (low certainty) to 124 541 US$ (moderate certainty). More data on long‐term safety are needed both for children and for adults, together with more efficacy data in the paediatric population. Registration: PROSPERO (CRD42020153645). [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis (AD) is one of the most prevalent skin diseases, but there are numerous knowledge gaps surrounding the impact this disease has on quality of life (QoL), mental health, and out-of-pocket expenses involved in the management of AD. The available scientific evidence on the multidimensional burden of AD is usually based on studies with measures reported by patients themselves., Methods: In this context, the MEASURE-AD trial was developed as a cross-sectional, multicenter, multinational trial using patient- and physician-reported measures to characterize the multidimensional burden of AD in adults with moderate-to-severe AD., Results: This paper presents the results of the Spanish cohort. We found that Spanish adults with moderate-to-severe AD and high EASI score (21.1-72) had a significantly increased disease burden, high severity of symptoms such as itch and sleep disturbances, impaired mental health and QoL, higher use of health care resources, and more out-of-pocket expenses than patients with low EASI scores (0-7 or 7.1-21)., Conclusions: This study provides information to better understand disease burden, and identify aspects to be improved in the management of AD., (Copyright © 2024 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.)

The 12-channel ECG is an important tool used for the diagnosis and treatment of various cardiac and other related diseases. The recording procedure requires the exact placement of 10 electrodes on the patients, because incorrect placement can lead to improper signals and, consequently, to false diagnoses. In addition, the placement of 10 electrodes is time consuming, often interferes with clinical processes, and is less patient-friendly. One possible solution could be the usage of a vector-based, 5-electrode, 12-lead monitoring ECG system (EASI). The aim of this work is to establish a quantitative comparison between the conventional 12-lead ECG and an EASI ECG by cross-correlating signals of the same type. For this purpose, we used a conventional 12-lead ECG device, Schwarzer Cardiotek GmbH; and an EASI device, Schwarzer Cardiotek GmbH. All instruments were made available by the company CRS medical GmbH. Both devices were simultaneously connected to an informed, healthy volunteer and signals were recorded under resting conditions. Crosscorrelation functions were calculated and analysed by using Matlab R2015a between the same original and filtered signal types, e.g. conventional and EASI lead I. Time lags between the recordings were compensated adequately. All signals, up to two conventional signals, were of high quality. We found a high degree of correlations between 10 of 12 leads (r > 0.9). However, the conventional recording system is more sensible to artifacts, muscle activities and noise, very likely due to its more complex electrode configuration and larger electrical sensing area. A visual inspection of the conventional and EASI time courses by an expert also indicated that EASI is useful in clinical practice. We compared a conventional 12-lead ECG with an EASI ECG by signal correlations. The results indicate that EASI is well suited for cardiologic routine: simplified electrode placement and reasonable signal quality. However, additional investigations are required, especially to test EASI for diagnostic purposes and with more sophisticated statistical methods.

In this paper, the fundamental problem for the full-duplex communication systems, i.e., self-interference cancellation (SIC), is investigated, and a novel digital-domain SIC method based on blind source separation is proposed. This method achieves SIC by separation and has two prominent characteristics that are: 1) it is a blind method, and no training sequence or time is needed and 2) it is unaffected by the nonlinear components of the self-interference signal. Meanwhile, the critical factors for spectral efficiency (SE) are fully analyzed herein. In the simulations, the performances of the proposed method, including SIC capacity, signal-to-interference-plus-noise ratio, SE, and SE gain, are comprehensively evaluated and compared with least-square-based SIC algorithms. These results show that the proposed algorithm can obtain considerable performances, even the best performance in some cases.

Atopic dermatitis (AD) severity measurement scales are important in clinical trials as objective outcome measures and are often required for government and private insurance plans. These scales are sometimes underused by clinicians due to a variety of factors including time constraints and lack familiarity. We conducted a literature review on the most commonly used AD measurement scales and provide succinct user guides and scoring explanations, advantages and disadvantages, and interscale comparisons. [ABSTRACT FROM AUTHOR]

Background: This article explores elder abuse in a hospitalised population. We wanted to identify details related to psychological and emotional abuse in the older population in our region and to determine the importance of the Elderly Abuse Suspicion Index (EASI©) in comprehensive geriatric assessments. Methods: This cross‐sectional study conducted between March 2015 and May 2016 included 386 consecutive hospitalised patients over 65 years of age. All patients underwent a geriatric assessment, data were collected about their medical history, and the EASI© was administered to each. The main outcome was identifying the presence, the type of abuse and the factors associated with abuse. Results: There were 21.5% of patients who suffered any form of abuse. Women were more frequently abused than men. Emotional abuse was the most common (60.2%) followed by neglect (53%) and physical abuse (22.91%); sexual abuse was absent in our study group. The abused patients had an impaired cognitive function (P = 0.034). They were also malnourished (P ≤ 0.001) and depressed (P = 0.001). The presence of peripheral artery disease, stroke, pneumonia, chronic kidney disease, musculoskeletal diseases and anxiety correlated with the presence of abuse. No statistically significant correlation was found between the degree of independence in instrumental activities of daily living and the presence of abuse (r = 0.105, P = 0.051). Conclusions: EASI is a tool for detecting elder abuse and should be included in the standard geriatric assessment to prevent ageism. The number of abused elderly patients is significant, and the multiple factors associated with abuse are diverse. [ABSTRACT FROM AUTHOR]