Evaluation of Inclusion and Exclusion Criteria for Pyoderma Gangrenosum in Clinical Research: A Systematic Review.

INTRODUCTION: Pyoderma gangrenosum (PG) is a rare, inflammatory dermatologic disease that, as a diagnosis of exclusion with nonspecific histologic features, is difficult to diagnose. As pharmaceutical interest in potential treatments for PG increases, the need for standardized diagnostic criteria to ensure reproducibility, comparability, and external validity of PG research is required. In this study, we aim to characterize the inclusion and exclusion criteria used in the diagnosis of PG in clinical research studies as well as the eligibility of PG in clinical trials. METHODS: A systematic review was conducted to characterize the PG inclusion and exclusion criteria in research studies. An additional search of the USA and international clinical trials databases was conducted as well to capture eligibility criteria for PG trials. RESULTS: Our study revealed a broad range of inclusion and exclusion criteria used to establish the presence or absence of PG. Based on eight distinct categories used to characterize inclusion criteria for research studies, diagnosis by a dermatologist (n = 25, 31.6%), no inclusion criteria listed (n = 21, 26.6%), and clinical and histopathologic features consistent with PG (n = 20, 25.3%) were most common. For current clinical trials, six categories were used to characterize inclusion criteria, of which clinical and histopathologic features consistent with PG (n = 5, 31.3%), identification based on diagnosis of PG (n = 4, 25.0%), and clinical features consistent with PG (n = 3, 18.8%) were the most common. CONCLUSION: This systematic literature review highlights the range of heterogeneity in diagnostic and eligibility criteria used in PG-directed clinical research and current clinical trials and illustrates the need for the development of consensus guidelines and a rigorous framework to enable high-quality future trials for PG.

Brigham Eyebrow Tool for Alopecia: A Reliable Assessment of Eyebrow Alopecia Areata.

There are no tools to evaluate eyebrow involvement in patients with alopecia areata. We developed and assessed the reliability of the Brigham Eyebrow Tool for Alopecia (BETA) as a quantitative evaluation of eyebrow alopecia areata. BETA uses facial landmarks of eyebrow anatomy and is calculated using surface area and density. A total of 50 eyebrow images with varying levels of hair loss were distributed to six board-certified dermatologists at three academic medical centers with standardized instructions and examples. Interrater and intrarater reliability were calculated using intraclass correlation coefficients (ICCs). BETA demonstrated high interrater (ICC = 0.88, confidence interval = 0.83-0.92 right eyebrow scores and ICC = 0.90, confidence interval = 0.85-0.94 left eyebrow scores) and intrarater (ICC = 0.90, confidence interval = 0.85-0.93 right eyebrow scores and ICC = 0.91, confidence interval = 0.87-0.94 left eyebrow scores) reliability. When measured in the same patient with varying degrees of hair loss over time, BETA demonstrated sensitivity to change. BETA is a simple and reliable objective assessment of eyebrow alopecia areata. BETA is easy-to-use and quick to calculate, making it feasible for a variety of clinical and research settings. Although developed for alopecia areata, we hope that BETA will be investigated in other etiologies of eyebrow alopecia to serve as a universal tool for monitoring disease progression, improvement, and response to treatment.

The Effects of Family Functioning on the Development of Posttraumatic Stress in Children and Their Parents Following Admission to the PICU.

OBJECTIVES: To report the rate of acute stress and posttraumatic stress among children and parents following PICU admission and the relation between family function and posttraumatic stress. DESIGN: Prospective, longitudinal, multi-informant observational study. Pediatric patients (n = 69) and parents were recruited in the ICU. They completed measures evaluating acute stress and posttraumatic stress during their hospitalization and at 3-month follow-up. Parents completed measures of family functioning during the hospitalization. Pearson correlations and multiple regression models were used to examine the relations between family functioning and acute stress and posttraumatic stress. SETTING: An academic, urban, pediatric hospital in California. PATIENTS: Children, 8-17 years old, admitted to the PICU for greater than 24 hours and their English- or Spanish-speaking parents. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All children endorsed acute stress during their PICU admission, with 51% meeting criteria for acute stress disorder. At 3-month follow-up, 53% of the children continued to endorse posttraumatic stress with 13% meeting criteria for posttraumatic stress disorder. Among parents, 78% endorsed acute stress during admission with 30% meeting criteria for acute stress disorder, and at follow-up, 35% endorsed posttraumatic stress with 10% meeting criteria for posttraumatic stress disorder. In multiple linear regression modeling, child acute stress significantly predicted child posttraumatic stress (ß = 0.36; p < 0.01). In the parent model, parent acute stress (ß = 0.29; p < 0.01) and parent education (ß = 0.59; p < 0.00) positively predicted parent's posttraumatic stress. Family function was not a predictor of either's posttraumatic stress. CONCLUSIONS: Both children and parents have alarmingly high rates of acute stress and posttraumatic stress following the child's PICU admission. Although family function did not emerge as a predictor in this study, further understanding of the influence of the family and the interplay between child and parent posttraumatic stress is needed to improve our understanding of the model of development of posttraumatic stress in this population to inform the intervention strategies.

Music-reading expertise modulates the visual span for English letters but not Chinese characters.

Recent research has suggested that the visual span in stimulus identification can be enlarged through perceptual learning. Since both English and music reading involve left-to-right sequential symbol processing, music-reading experience may enhance symbol identification through perceptual learning particularly in the right visual field (RVF). In contrast, as Chinese can be read in all directions, and components of Chinese characters do not consistently form a left-right structure, this hypothesized RVF enhancement effect may be limited in Chinese character identification. To test these hypotheses, here we recruited musicians and nonmusicians who read Chinese as their first language (L1) and English as their second language (L2) to identify music notes, English letters, Chinese characters, and novel symbols (Tibetan letters) presented at different eccentricities and visual field locations on the screen while maintaining central fixation. We found that in English letter identification, significantly more musicians achieved above-chance performance in the center-RVF locations than nonmusicians. This effect was not observed in Chinese character or novel symbol identification. We also found that in music note identification, musicians outperformed nonmusicians in accuracy in the center-RVF condition, consistent with the RVF enhancement effect in the visual span observed in English-letter identification. These results suggest that the modulation of music-reading experience on the visual span for stimulus identification depends on the similarities in the perceptual processes involved.

Risk Factors and Effects of Care Management on Hospital Readmissions Among High Users at an Academic Medical Center.

Few studies have examined predictors of hospital readmission among high-using patients enrolled in a behaviorally oriented intensive care management program. The purpose of this case control study was to describe risk factors and the effectiveness of a complex care management program for hospital readmission among vulnerable patients at a large academic medical center. One hundred sixty-three patients enrolled in the University of Michigan Complex Care Management Program (UM CCMP) were hospitalized between January 2014 and March 2015. Sixty were readmitted within 30 days of discharge. Among all patients, the mean age was 51.1 years, 38.7% were non-White, 81.5% had Medicaid and/or Medicare, 50.3% were without stable housing, and 27.6% had significant psychiatric illnesses. Although mostly not statistically significant, multivariable risk of readmission was increased by having twice the mean number of hospitalizations in the last 6 months (odds ratio [OR] = 1.44, 95% CI [1.00, 2.06]), having chronic pain on a scheduled narcotic (OR = 1.49, 95% CI [0.67, 3.35]), and going to a primary care physician within 30 days of discharge (OR = 1.35, 95% CI [0.63, 2.89]). Risk was decreased by going to a specialist (OR = 0.54, 95% CI [0.23, 1.27]) and receiving moderate-intensity CCMP intervention (OR = 0.48, 95% CI [0.20, 1.19]). Among hospitalized high-using patients enrolled in the UM intensive care management program, readmission is likely significantly influenced by medical, behavioral, and social challenges. Care management appears most effective in preventing readmission among patients with mid- rather than high- or low-level needs. These findings at a single program should be explored in further, larger studies.

Multi-domain neurocognitive impairment following definitive intensity-modulated radiotherapy for nasopharyngeal cancer: A cross-sectional study.

INTRODUCTION: Neurocognitive impairment from inadvertent brain irradiation is common following intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC). This study aimed to determine the prevalence, pattern, and radiation dose-toxicity relationship of this late complication. MATERIALS AND METHODS: We undertook a cross-sectional study of 190 post-IMRT NPC survivors. Neurocognitive function was screened using the Montreal Cognitive Assessment-Hong Kong (HK-MoCA). Detailed assessments of eight distinct neurocognitive domains were conducted: intellectual capacity (WAIS-IV), attention span (Digit Span and Visual Spatial Span), visual memory (Visual Reproduction Span), verbal memory (Auditory Verbal Learning Test), processing speed (Color Trail Test), executive function (Stroop Test), motor dexterity (Grooved Pegboard Test) and language ability (Verbal Fluency Test). The mean percentiles and Z-scores were compared with normative population data. Associations between radiation dose and brain substructures were explored using multivariable logistic regression. RESULTS: The median post-IMRT interval was 7.0 years. The prevalence of impaired HK-MoCA was 25.3 % (48/190). Among the participants, 151 (79.4 %) exhibited impairments in at least one neurocognitive domain. The predominantly impaired domains included verbal memory (short-term: mean Z-score, -0.56, p < 0.001; long-term: mean Z-score, -0.70, p < 0.001), processing speed (basic: mean Z-score, -1.04, p < 0.001; advanced: mean Z-score, -0.38, p < 0.001), executive function (mean Z-score, -1.90, p < 0.001), and motor dexterity (dominant hand: mean Z-score, -0.97, p < 0.001). Radiation dose to the whole brain, hippocampus, and temporal lobe was associated with impairments in executive function, verbal memory, processing speed, and motor dexterity. CONCLUSIONS: Neurocognitive impairment is prevalent and profound in post-IMRT NPC survivors. Cognitive assessment and rehabilitation should be considered part of survivorship care.

Eligibility Criteria for Active Ulcerative Pyoderma Gangrenosum in Clinical Trials: A Delphi Consensus on Behalf of the UPGRADE (Understanding Pyoderma Gangrenosum: Review and Assessment of Disease Effects) Group.

At present, there are no standardized guidelines for determining patient eligibility for pyoderma gangrenosum (PG) clinical trials. Thus, we aim to determine which clinical features, histopathological features, or laboratory features should be included in active ulcerative PG clinical trial eligibility criteria for treatment-naïve patients and patients already treated with immunomodulating medications (treatment-exposed patients). This study employed 4 rounds of the Delphi technique. Electronic surveys were administered to 21 international board-certified dermatologists and plastic surgeon PG experts (June 2022-December 2022). Our results demonstrated that for a patient to be eligible for a PG trial, they must meet the following criteria: (i) presence of ulcer(s) with erythematous/violaceous undermining wound borders, (ii) presence of a painful or tender ulcer, (iii) history/presence of rapidly progressing disease, (iv) exclusion of infection and other causes of cutaneous ulceration, (v) biopsy for H&E staining, and (vi) a presence/history of pathergy. These criteria vary in importance for treatment-naïve versus treatment-exposed patients. Given the international cohort, we were unable to facilitate live discussions between rounds. This Delphi consensus study provides a set of specific, standardized eligibility criteria for PG clinical trials, thus addressing one of the main issues hampering progress toward Food and Drug Administration approval of medications for PG.

Experiencing Workplace Bullying in Patients with Alopecia Areata: A Cross-Sectional Survey Study.

Introduction: Alopecia areata (AA) is an immune-mediated hair loss condition with substantial psychosocial impact. The impact of AA on social interactions at work has not been established. Methods: We administered the Negative Acts Questionnaire-Revised Scale to the National Alopecia Areata Foundation database to evaluate workplace bullying in patients with AA. Results: Ultimately, 673/1,120 individuals who met inclusion criteria completed the survey. Most respondents were female (n = 537, 79.8%), Caucasian (n = 508, 75.5%), with an average age of 46.8 ± 14, and employed full-time (n = 427, 63.4%). Our results demonstrate 21.7% (n = 146) of respondents experienced workplace bullying. Participants most frequently faced having their opinions ignored (53.8%, n = 362), being excluded (47.7%, n = 321), and having gossip spread about them (44.0%, n = 296). Notably, 75.0% (n = 120/160) of individuals who self-reported bullying addressed the behavior; however, 30.8% of participants noted the bully continued (30.8%, n = 37). Stress associated with filing a complaint (43.5%, n = 293) and effect on future career options (36.1%, n = 243) were common barriers to report bullying. Conclusion: This study expands our understanding of the psychosocial impact of AA by confirming individuals with AA experience workplace bullying. Stigma against patients may play a role in this phenomenon. Future work is warranted to identify strategies to reduce bullying against patients with AA.

Post-Traumatic Stress Disorder in Patients with Alopecia Areata: A Survey Study in the USA.

Introduction: Alopecia areata (AA) is an autoimmune condition that results in nonscarring hair loss. AA is comorbid with mental health disorders including anxiety and depression. This study aimed to evaluate the presence of post-traumatic stress disorder (PTSD) in relation to hair loss in patients with AA. Methods: A cross-sectional national survey was distributed using the National Alopecia Areata Foundation's (NAAF) email list. This study was approved by the Mass General Brigham Institutional Review Board. Participants were asked to complete the PTSD Checklist for the DSM-5 (PCL-5), a validated screening tool for PTSD in the context of their AA. Results: Of the 1,449 completed surveys (completion rate 79.6%), most respondents were female (83.8%) and white (76.6%) with an average age of 50.6 ± 15.6 years. Respondents had AA for an average of 17.7 ± 15.8 years, with 91.4% experiencing current active hair loss. A total of 33.9% of respondents screened positively for PTSD, with an average score of 48.8 ± 12.3 on the PCL-5 in participants who screened positively. Participants with alopecia totalis have the highest average PCL-5 score of 30.1 ± 19.2, followed by participants with alopecia universalis with an average score of 26.0 ± 19.9, and lastly patchy AA with an average score of 24.5 ± 18.3 (p = 0.003). Feelings of intrusion and avoidance were the predominant reported symptoms. Total PTSD scores were significantly higher in respondents who were younger and identified as Black or African American and Hispanic when compared to white and non-Hispanic respondents, respectively. Conclusion: These findings identify that one in 3 patients with AA in this cohort meet the screening criteria for PTSD specifically relating to their hair loss experience. These results further highlight the mental health comorbidities associated with AA and emphasize that these symptoms may persist even after hair regrowth. Limitations include the nonrandomized NAAF population with most participants being white females. Future studies should confirm these findings in other patient populations. Finally, respondent's baseline mental health was not assessed; therefore, a causal relationship between AA and PTSD cannot be deduced.

An Assessment of Current Clinician-Reported and Patient-Reported Outcome Measures for Alopecia Areata: A Scoping Review.

Although progress has been made in developing outcome measures for AA, the use of these measures remains unstandardized. A scoping review was conducted to identify the clinician-reported outcome measures (ClinROMs) and patient-reported outcome measures (PROMs) used in assessing and treating AA, the results of which revealed heterogeneity in AA outcome measures. Of 23 research studies ultimately included, only 2 ClinROMs were used by >15% of studies; likewise, of 110 clinical trials evaluated, numerous outcome instruments were used, but only one ClinROM was used by >5% of trials (Severity of Alopecia Tool). These results suggest the need for consensus and standardization in both research and trial settings.

Factors influencing alopecia areata treatment decisions: A qualitative assessment.

Background: Alopecia areata (AA) is a disease of hair loss in which patients may benefit from comprehensive understanding of AA's disease process and therapeutic options during treatment decision-making. Objective: Determine factors influencing patients' AA treatment decision-making. Methods: Qualitative interviews were conducted using semi-structured interview guides. Interviews were coded using inductive thematic analysis. Results: Twenty-one participants with AA were interviewed. Coding interrater reliability was κ = 0.87-0.91, indicating strong-almost perfect agreement. Participants faced multiple barriers, including lack of access to health care (n = 10, 47.6%) and lack of transparency about their condition and treatment options (n = 9, 42.9%). Information about AA was sought from primarily the internet (n = 15, 71.4%) and physician recommendation (n = 15, 71.4%). When choosing AA treatments, patients often considered treatment efficacy (n = 21, 100%), safety (n = 21, 100%), and convenience of use (n = 20, 95.2%). Limitations: Referral and regional biases may be present and limit generalizability. Conclusions: Patients with AA face various challenges including medical uncertainty and lack of information. Patients need trustworthy and accessible sources of information regarding their treatment that also take into consideration their preferences and values.

Physician values in alopecia areata treatment decision-making: A qualitative assessment.

Background: Alopecia areata (AA) is a disease of hair loss with multiple treatment options. Physicians play an important role in guiding patients during the decision-making process. Objective: Assess physicians' values and attitudes when helping patients choose an AA treatment. Methods: Semi-structured qualitative interviews were conducted with dermatologists of varying practice type and location. Each interview was coded independently twice using inductive thematic analysis. Interrater reliability and code frequencies were determined. Results: Fourteen participants were interviewed. Interrater reliability was κ = 0.85 to 0.97. Dermatologists wanted patients to consider various treatment factors (ie, efficacy, safety, convenience of use, accessibility) and also assessed patients' AA clinical severity and personality traits. Participants often encountered various barriers to effective communication with patients, which may be mitigated by shared decision-making. Shared decision-making tools were perceived to potentially improve patient care and communication, although physicians expressed concern about lack of individualization, limitations of time, and the appropriateness of information. Conclusion: AA treatment decision-making is a complex process that often utilizes the expertise of a dermatologist, during which shared decision-making tools may be of value to both patients and physicians.

Music reading experience modulates eye movement pattern in English reading but not in Chinese reading.

Here we tested the hypothesis that in Chinese-English bilinguals, music reading experience may modulate eye movement planning in reading English but not Chinese sentences due to the similarity in perceptual demands on processing sequential symbol strings separated by spaces between music notation and English sentence reading. Chinese-English bilingual musicians and non-musicians read legal, semantically incorrect, and syntactically (and semantically) incorrect sentences in both English and Chinese. In English reading, musicians showed more dispersed eye movement patterns in reading syntactically incorrect sentences than legal sentences, whereas non-musicians did not. This effect was not observed in Chinese reading. Musicians also had shorter saccade lengths when viewing syntactically incorrect than correct musical notations and sentences in an unfamiliar alphabetic language (Tibetan), whereas non-musicians did not. Thus, musicians' eye movement planning was disturbed by syntactic violations in both music and English reading but not in Chinese reading, and this effect was generalized to an unfamiliar alphabetic language. These results suggested that music reading experience may modulate perceptual processes in reading differentially in bilinguals' two languages, depending on their processing similarities.