Search

Background: Dermatomyositis (DM) is a rare and severely debilitating autoimmune disease that can affect children and adults; however, there is little understanding of the patient-reported experience and uncertainty around validated clinical outcomes assessments (COAs) that could measure changes in the condition during clinical trials of new treatments., Objectives: The aim of this study was to understand the patient experience of DM, with a focus on its cutaneous manifestations, to describe the patient experience and determine the suitability of existing COA measures., Methods: Adult (≥ 18 years) patients (N = 28) with severe active cutaneous manifestations of DM were interviewed. In the 90-min interviews, open-ended questions and probes were used to elicit descriptions of key clinical manifestations and patients' experiences of DM, including the symptoms and impacts on their daily lives and wellbeing., Results: Patients reported 13 different skin manifestations of DM. The most common were rash (n = 28, 100%), itch (n = 28, 100%), dry skin (n = 23, 82%), and swelling of the skin (n = 17, 61%). The head and face, followed by hands, were perceived as the most bothersome body areas affected by skin manifestations, because they are exposed and visible to themselves and other people. All patients (n = 28, 100%) reported at least one impact of DM, which varied greatly between patients, but included emotional, psychological, cognitive, and physical impacts, and those affecting daily life, such as work and sleep. Over half of the patients (n = 19, 67%) reported that their daily activities were impacted by DM., Conclusions: The qualitative interviews with patients revealed that the presentation of DM manifestations is highly variable but affects patients' emotional wellbeing, physical activities, and daily life significantly., (© 2024. The Author(s).)

Background: Pruritus is a common, bothersome symptom for patients with mild-to-moderate plaque psoriasis (PsO), yet no validated scale assesses it in this patient population. We aimed to validate the Peak Pruritus-Numerical Rating Scale (PP-NRS) using data from a Phase 2b study investigating the efficacy of brepocitinib in patients with mild-to-moderate chronic PsO., Methods: Patients completed the PP-NRS daily from baseline for the first 2 weeks after the dose administration and subsequently only on visit days. Test-retest reliability (intraclass correlation coefficient [ICC]), construct validity (known group validity and convergent validity), ability to detect change, and meaningful within-patient change (MWPC) were evaluated using correlation and regression analyses., Results: The PP-NRS demonstrated acceptable test-retest reliability (ICC: 0.86-0.89). Known-group evidence demonstrated that PP-NRS scores could discriminate between different degrees of disease severity. Convergent validity was supported by significant correlation coefficients between the PP-NRS and Patient Global Assessment (PtGA), Dermatology Life Quality Index, and Psoriasis Symptom Inventory, which generally exceeded 0.50. The ability to detect change was evidenced by an approximately linear relationship between changes in PP-NRS and Physician Global Assessment or PtGA of psoriasis scores. The value of 2.8 was determined as the MWPC for the PP-NRS., Conclusions: PP-NRS is a reliable, practical test for assessing pruritus in mild-to-moderate PsO clinical trials., Gov Identifier: NCT03850483., (© 2024 the International Society of Dermatology.)

Introduction: Dermatomyositis (DM) is a rare systemic autoimmune disease characterized by a distinctive debilitating skin rash and skeletal muscle weakness. It is unclear if existing clinical outcome assessment (COA) measures include the concepts of priority to patients and those necessary to fully capture improvements in the active cutaneous manifestations of DM. This study aimed to develop the Cutaneous Dermatomyositis Investigator Global Assessment (CDM-IGA), a de novo IGA, for use in clinical trials of adult DM., Methods: Eight DM clinical experts participated in 60-min qualitative interviews consisting of concept elicitation and cognitive debriefing methodologies. Concept elicitation comprised open-ended questions with follow-up probes to explore clinicians' experiences of treating patients with DM, the impact of symptoms on patients' quality of life, and the severity levels of disease characteristics to explore DM progression. Cognitive debriefing required the clinical experts to perform a review of the CDM-IGA, designed to assess the severity of cutaneous disease activity of DM. After the interviews, a consensus meeting with three clinical experts was held to agree on any outstanding issues relating to the CDM-IGA., Results: The CDM-IGA was iteratively developed using the opinions of nine clinical experts. Feedback provided by all clinicians agreed that erythema was the main active cutaneous manifestation of DM and should be the primary characteristic on the CDM-IGA, split by erythema color and extent. To determine cutaneous disease severity, experts suggested adding a metric called secondary changes, which combined erosion/ulceration and lichenification, which could modify the patient's final score. Three clinical experts suggested that a photo-guide to support assessments of erythema across different skin tones could be beneficial., Conclusions: A novel CDM-IGA was developed for use with adult patients with DM in clinical trials, based on an iterative development process that combined qualitative feedback from clinical experts of DM and importantly adult patients living with DM., (© 2024. The Author(s).)

Purpose: Topical treatments for mild-to-moderate (MM) atopic dermatitis (AD) include emollients, corticosteroids, calcineurin inhibitors, a Janus kinase inhibitor, and a phosphodiesterase 4 inhibitor, which differ in multiple ways. This study aimed to quantify the conditional relative importance (CRI) of attributes of topical treatments for MM AD among adult and adolescent patients and caregivers of children with MM AD. Materials and methods: A discrete-choice experiment (DCE) survey was administered to US adults and adolescents with MM AD and caregivers of children with MM AD. Each choice task comprised 2 hypothetical topical treatments characterized by efficacy, adverse events, vehicle, and application frequency. Data were analyzed using a random-parameters logit model to calculate the CRI of each attribute. Results and conclusions: 300 adults, 331 adolescents, and 330 caregivers completed the DCE. Avoiding changes in skin color (CRI 29.0) and time until itch improves (26.6) were most important to adults, followed by time until clear/almost clear skin (17.8). Application frequency (3.0) did not have a statistically significant impact on adults' choices. Adolescents were less concerned about changes in skin color than adults or caregivers; caregivers were less concerned about time until clear/almost clear skin than patients. Physicians should consider age-relevant aspects of preferences in treatment discussions with patients and caregivers.

Traumatic brain injury (TBI) is a complex and heterogeneous condition that can cause wide-spectral neurological sequelae such as behavioral deficits, sleep abnormalities, and post-traumatic epilepsy (PTE). However, understanding the interaction of TBI phenome is challenging because few animal models can recapitulate the heterogeneity of TBI outcomes. We leveraged the genetically diverse recombinant inbred Collaborative Cross (CC) mice panel and systematically characterized TBI-related outcomes in males from 12 strains of CC and the reference C57BL/6J mice. We identified unprecedented extreme responses in multiple clinically relevant traits across CC strains, including weight change, mortality, locomotor activity, cognition, and sleep. Notably, we identified CC031 mouse strain as the first rodent model of PTE that exhibit frequent and progressive post-traumatic seizures after moderate TBI induced by lateral fluid percussion. Multivariate analysis pinpointed novel biological interactions and three principal components across TBI-related modalities. Estimate of the proportion of TBI phenotypic variability attributable to strain revealed large range of heritability, including >70% heritability of open arm entry time of elevated plus maze. Our work provides novel resources and models that can facilitate genetic mapping and the understanding of the pathobiology of TBI and PTE., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Background: Atopic dermatitis (AD) is a prevalent inflammatory, pruritic skin disease. The Janus kinase (JAK) pathway is a treatment target., Objectives: To assess the efficacy, safety and pharmacokinetics of topical cream brepocitinib, a small-molecule tyrosine kinase 2 (TYK2)/JAK1 inhibitor, in participants with mild-to-moderate AD., Methods: In this phase IIb, double-blind, dose-ranging study, participants were randomized to receive one of eight treatments for 6 weeks: brepocitinib 0·1% once daily (QD), 0·3% QD or twice daily (BID), 1·0% QD or BID, 3·0% QD, or vehicle QD or BID. The primary endpoint was the percentage change from baseline in the Eczema Area and Severity Index (EASI) total score at week 6. Adverse events (AEs) were monitored., Results: Overall, 292 participants were enrolled and randomized. The brepocitinib 1% QD and 1% BID groups achieved statistically significantly greater (with multiplicity-adjusted P < 0·05 due to Hochberg's step-up method) percentage reductions from baseline in EASI total score at week 6 [least squares mean (90% confidence interval, CI): QD: -70·1 (-82·1 to -58·0); BID: -75·0 (-83·8 to -66·2)] compared with respective vehicle [QD: -44·4 (-57·3 to -31·6); BID: -47·6 (-57·5 to -37·7)]. There was not a dose-dependent trend in AE frequency, and there were no serious AEs or deaths., Conclusions: Topical brepocitinib is effective and well tolerated in participants with mild-to-moderate AD. What is already known about this topic? Janus kinase (JAK) inhibitors are in development for treatment of atopic dermatitis (AD). The tyrosine kinase 2 and JAK 1 inhibition by brepocitinib may bring a new profile for topical JAK inhibitors for treatment of mild-to-moderate AD. What does this study add? Topical brepocitinib can provide rapid, effective symptom reduction, and could offer a novel alternative to current topical treatments for mild-to-moderate AD., (© 2022 Pfizer Inc and The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Introduction: Comparative data on the economic burden of alopecia areata relative to the general population are limited. The objective of this retrospective database analysis was to evaluate healthcare resource utilization and direct medical costs among patients with alopecia areata from the US payer perspective compared with matched controls., Methods: Validated billing codes were used to identify patients with alopecia areata from the IQVIA PharMetrics Plus (2016-2018) who had continuous pharmacy and medical enrollment for 365 days both before (baseline period) and after (evaluation period) the index date. Demographic and clinical characteristics were characterized, and baseline comorbidities were assessed with the Quan Charlson Comorbidity Index., Results: Using the exact matching feature from Instant Health Data, 14,340 patients with alopecia areata were matched with 42,998 control patients aged ≥ 12 years. Patients with alopecia areata had higher healthcare resource utilization and adjusted total all-cause mean medical costs versus matched controls ($8557 versus $6416; p < 0.0001), because of higher inpatient costs, emergency department visits, ambulatory visits, number of prescriptions and prescription costs, and other costs such as durable medical equipment and home healthcare. The number of inpatient visits did not significantly differ between the two groups. Mean ambulatory costs were $3640 for patients with alopecia areata and $2062 for controls, and mean pharmacy costs were $3287 and $1843, respectively (p < 0.0001 for both). Pharmacy costs related to immunologic agents represented 50.0% of the total difference in pharmacy spending between patients with alopecia areata and controls. Surgery on the integumentary system accounted for 9.5% of the total difference in ambulatory costs., Conclusion: Alopecia areata is associated with significant incremental healthcare resource utilization and costs relative to matched controls due to increased spending in areas such as surgical procedures and psychological and pharmacological interventions. Costs are primarily driven by ambulatory and pharmacy spending., (© 2022. The Author(s).)

Background: Moderate-to-severe atopic dermatitis (AD) is inadequately controlled with current treatments for many patients. Abrocitinib is an oral Janus kinase 1 selective inhibitor under investigation for the treatment of AD., Objective: The aim of the study was to evaluate patient-reported outcomes in a phase 2b study of abrocitinib in adults with moderate-to-severe AD inadequately controlled by topical therapy (NCT02780167)., Methods: Patients (N = 267) were randomly assigned 1:1:1:1:1 to 12-week, once-daily abrocitinib (200, 100, 30, 10 mg) or placebo. Patient-reported outcomes included pruritus numeric rating scale (average), Patient Global Assessment, Patient-Oriented Eczema Measure, Pruritus and Symptoms Assessment for AD, Dermatology Life Quality Index, and Hospital Anxiety and Depression Scale (HADS)., Results: Abrocitinib 200 or 100 mg resulted in significantly greater improvements from baseline versus placebo in peak pruritus numeric rating scale (by days 2 and 3, respectively), Patient-Oriented Eczema Measure, Pruritus and Symptoms Assessment for AD, Dermatology Life Quality Index, and HADS (200 mg only, by week 1 or 2), and proportions of the patients with Patient Global Assessment clear/almost clear with 2-point or greater improvement (by weeks 1 and 4, respectively) that continued through week 12 (except HADS)., Conclusions: Abrocitinib treatment resulted in rapid (2 days to 2 weeks) and persistent improvements in AD symptoms and impacts in moderate-to-severe disease., (Copyright © 2021 American Contact Dermatitis Society. All Rights Reserved.)

Introduction: Alopecia areata (AA) is a chronic, autoimmune disease of hair loss, which can significantly affect the emotional and psychological well-being of patients. A systematic literature review was conducted to better understand the burden of AA from the patient perspective., Methods: Embase, MEDLINE and Cochrane databases were searched for published studies (2008-2018) reporting on assessments of health-related quality of life (HRQoL) for patients with AA. Qualitative, and quantitative data were collected., Results: The review included 37 studies encompassing a range of clinical outcome assessment (COA) tools. None of the COA tools were specific for AA, and only one study used the Hairdex scale, which was designed to evaluate HRQoL in patients with disorders of the hair and scalp. All studies reported substantial impact on HRQoL due to AA, both overall and in domains related to personality (i.e. temperament and character), emotions and social functioning. Acute stress was also noted, and several studies identified lack of emotional awareness (alexithymia) in 23-50% of the patients with AA., Conclusions: Although it is well-established that patients with AA experience anxiety and depression, they also experience a decrease in HRQoL in many other areas, including personality, emotions, behaviors and social functioning, and these changes may be accompanied by acute stress and alexithymia. There is a need to achieve consensus on a core set of measures for AA and to develop and validate AA-specific measurement tools for use in future studies, to attain a clearer understanding of the impact of AA on patients., Trial Registration: PROSPERO registration number; CRD42019118646.

Introduction: For many, atopic dermatitis (AD) is not adequately controlled with topical regimens. This analysis examined treatment using advanced therapies and associated costs., Methods: The IQVIA Health Plan Claims data set was analyzed. Patients aged ≥ 12 years with AD who newly initiated advanced therapy after the availability of dupilumab (March 28, 2017) and had ≥ 6 months continuous enrollment before and after their first advanced therapy claim (index date) were included. Advanced therapies included dupilumab, systemic corticosteroids (SCSs), systemic immunosuppressants (SISs), and phototherapy. A multivariate regression model was used to predict annualized follow-up healthcare costs., Results: In total, 1980 patients were included (61.1% female; mean age, 41.2 years [SD, 17.4]; 11.3% < 18 years). Pre-index date, 65.2% of patients used topical corticosteroids (TCSs; 40.7% and 32.1% used medium and high potency, respectively). The most common advanced therapy was SCSs (N = 1453 [73.4%]; 69.2% prednisone) followed by dupilumab (N = 265 [13.4%]), SISs (N = 99 [5.0%]; 47.5% methotrexate), and phototherapy (N = 163 [8.2%]). Of patients treated with dupilumab, SISs, and phototherapy, 17.4%, 26.3%, and 14.1%, respectively, were prescribed SCSs post-index date. Overall, 62.6% of patients initiating SCSs, 49.1% initiating dupilumab, 64.6% initiating SISs, and 36.2% initiating phototherapy were prescribed TCSs post-index date. Mean annualized total costs (SD) post-index date were $20,722 ($47,014): $11,196 ($41,549) in medical costs ($7973 [$35,133] in outpatient visit costs) and $9526 ($21,612) in pharmacy costs. Mean annualized total cost (SD) varied significantly (P < 0.05) by index treatment: dupilumab, $36,505 ($14,028); SCSs, $17,924 ($49,019); SISs, $24,762 ($47,583); phototherapy, and $17,549 ($57,238)., Conclusions: Switching to combination therapy with SCSs and TCSs was common within 6 months of initiating advanced therapy in patients with AD. Patients also incurred significant pharmacy and outpatient costs. These results highlight the difficulty of managing AD with these existing treatment options.

Background: Technology and social media offer individuals with intellectual and/or developmental disabilities (I/DD) unique and innovative ways to facilitate active participation in their own healthcare process. What remains unclear is the extent to which devices are currently used by this growing patient population., Objective: To explore the prevalence of technology and social media use, as well as the possible barriers, among adult patients with I/DD., Methods: A cross-sectional study utilizing an anonymous, accessible survey was used to obtain data from all adult patients (18 + years of age) with I/DD presenting for primary care services at a healthcare facility in New York between September and December of 2016., Results: A total of 370 individuals completed the survey (529 approached, 69.9% response rate). Less than half (44.6%) of respondents used devices such as a tablet, smartphone or desktop; most (86.8%) did not use social media. Only 21.6% of respondents indicated that they use some type of assistive technology. While some respondents (46.0%) were identified by their caregivers as having a disability that would prevent them from learning/using technology, other respondents reported having no challenges (18.0%), needing training and/or ongoing support (7.4%), or being uncertain as to whether they would experience any challenges (15.5%)., Conclusions: Many adult patients with I/DD do not use technology and social media that could promote self-determination and participation in their healthcare. Continued efforts must be made to promote technology use among adults with I/DD and to ensure that appropriate training is available for both the individual and his/her caregivers to achieve adoption and utilization., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To understand the patient-influenced activities and characteristics associated with return to a single postacute care transitional care clinic visit in a cohort of patients cared for at the test health system site of the larger Comprehensive Post-Acute Stroke Services (COMPASS) cluster randomized trial., Design: Retrospective cohort., Setting: A large health system., Participants: Patients discharged directly home between June 2016 and June 2018 after sustaining a stroke who did not receive formal inpatient rehabilitation services while being cared for in a single comprehensive stroke center, defined as a center that meet standards to rapidly diagnose and treat the most complex stroke cases., Interventions: Study participants had the opportunity to participate in a (1) 2-day call, (2) comprehensive care transitions clinic visit, and (3) individualized care plan., Main Outcome Measures: Patient participation in a single postacute care comprehensive care transitions visit, ideally completed within 7-14 calendar days post discharge vs not attending this visit. Care transition visits are where the responsibility for preventive care, other services, and posthospital follow-up are transitioned to outpatient providers., Results: Among 1300 eligible patients (mean age 64.8 years; 45% female; 25.4% nonwhite; 9.7% uninsured), 95.7% had follow-up clinic visits scheduled before discharge, 22.6% received home health referrals before discharge, 60.2% completed the 2-day call, and 63.2% attended the COMPASS visit. Among attendees, 33.2% attended by day 14, 71.3% attended within 30 days, and 28.7% attended after day 30. The median driving distance to the COMPASS visit was 45.9 miles or 73.9 km. Odds of visit attendance were higher if COMPASS 2-day follow up calls were completed, if follow-up clinic appointments were scheduled before discharge, if the patient had a primary care provider, and if the patients experienced a stroke vs a transient ischemic attack. Additionally, when we used the number of referrals at hospital discharge for different types of outpatient therapy as a surrogate marker of poststroke impairment, patients having no therapy referrals (milder to no impairments) had lower odds of attending the COMPASS visit than those with 1 therapy referral. Likewise, those with more than 1 referral were also less likely to attend the COMPASS visit., Conclusions: This analysis highlights that scheduling visits at discharge and completing timely telephone follow-up shortly after discharge may lead to greater adherence to in-person clinic follow-up after stroke., (© 2019 The Authors.)

Background: Increased toxicities have been identified with higher doses of pegaspargase (PEG-ASP) in adults. This has led to routine use of a dose cap of 3,750 IU for adult acute lymphoblastic leukemia (ALL) patients in most institutions. In pediatric ALL patients, PEG-ASP is not capped. There is concern at our institution that larger doses may result in increased rates of adverse effects and that increased monitoring may be warranted in pediatric patients receiving doses greater than 3,750 IU. The objective of this study is to quantify the difference in the rates of PEG-ASP-associated adverse events between pediatric patients who received doses greater than 3,750 IU and less than or equal to 3,750 IU., Methods: Retrospective chart review of patients 1-21 years old with pre-B-cell ALL who received PEG-ASP between 2007 and 2014 at an academic medical center., Results: Of 183 patients included in the analysis, 24 received PEG-ASP doses higher than 3,750 IU and 159 received doses less than or equal to 3,750 IU. The incidence of venous thromboembolism (VTE) was significantly higher for patients in the group that received more than 3,750 IU compared with those who received 3,750 IU or less (20.8 vs. 1.89%, respectively; P = 0.0011). The incidence of pancreatitis (P = 0.0306) and hyperglycemia (P = 0.0089) were also higher in the group that received more than 3,750 IU., Conclusions: PEG-ASP doses higher than 3,750 IU are associated with higher rates of VTE, pancreatitis, and hyperglycemia in pediatric patients with pre-B-cell ALL. Patients receiving more than 3,750 IU should have increased monitoring, and larger, multicenter trials are needed to determine if monitoring, VTE prophylaxis, and potential dose capping recommendations should be added to clinical trial protocols., (© 2017 Wiley Periodicals, Inc.)

Complex human traits are influenced by variation in regulatory DNA through mechanisms that are not fully understood. Because regulatory elements are conserved between humans and mice, a thorough annotation of cis regulatory variants in mice could aid in further characterizing these mechanisms. Here we provide a detailed portrait of mouse gene expression across multiple tissues in a three-way diallel. Greater than 80% of mouse genes have cis regulatory variation. Effects from these variants influence complex traits and usually extend to the human ortholog. Further, we estimate that at least one in every thousand SNPs creates a cis regulatory effect. We also observe two types of parent-of-origin effects, including classical imprinting and a new global allelic imbalance in expression favoring the paternal allele. We conclude that, as with humans, pervasive regulatory variation influences complex genetic traits in mice and provide a new resource toward understanding the genetic control of transcription in mammals.