34631 Do patients with vitiligo and health care professionals treating them recognize the burden in living with the disease in the United States? Findings from the VALIANT study

Vitiligo is a chronic autoimmune disease characterized by the destruction of melanocytes, resulting in pale or white patches of skin. The population-based Vitiligo and Life Impact Among International Communities (VALIANT) study sought to understand the impact and burden of vitiligo on quality of life (QoL) from the patient and physician perspective from around the world. The VALIANT study recruited adult participants (aged ≥18 years who self-reported a vitiligo diagnosis) via an online panel. Participants were asked questions regarding their mental health, psychosocial burden, and behavior in professional and social situations. Separately, health care professionals (HCPs; physicians, nurse practitioners, or physician assistants) who treat patients with vitiligo completed an online-based questionnaire. In the United States, 608 patients and 250 HCPs (166 dermatologists and 84 primary care providers) participated in the survey. Confidence in the ability to improve QoL and long-term psychological outcomes of their patients with vitiligo was noted in 67% and 58% of HCPs, respectively. HCPs and patients were asked the same questions regarding avoidance/impact behaviors; concordance was achieved on items such as wearing certain clothing to cover vitiligo lesions and avoiding going to beach/pool/social events. However, HCPs often underestimated the impact of vitiligo compared with the patient’s perspective in other areas, such as making career choices (33% vs 51%), managing other medical diseases (25% vs 49%), and obtaining other preventive care (20% vs 49%). In summary, increased understanding between HCPs and patients with vitiligo regarding a holistic understanding of the psychological burden and mental health of patients is needed

34612 Exploring the natural history of vitiligo in the United States: Findings from the VALIANT study

Vitiligo is a chronic autoimmune disease characterized by the destruction of melanocytes, resulting in depigmented skin lesions. Epidemiology studies in vitiligo are often limited to smaller sample sizes and rely on dermatology clinics as the source population. The population-based Vitiligo and Life Impact Among International Communities (VALIANT) study sought to understand the natural history of vitiligo among patients around the world. Here, data from US participants are presented. Participants were recruited via an online panel. Adults (aged ≥18 years) who self-reported a vitiligo diagnosis by a health care professional were eligible to participate. Of 608 US patients, 58% were male; median (range) age at the time of the survey was 36 (18–83) years. Mean disease duration was 11 years, with a mean 1.6 years between first noticing lesions and achieving a formal diagnosis. More than one-third of patients were previously misdiagnosed (37%), with higher rates among patients with darker skin types (67% for Fitzpatrick types IV–VI). Nearly two-thirds (62%) directly sought treatment for vitiligo; vitiligo was an incidental finding in the remaining 38%. Nearly two-thirds (64%) were diagnosed by a dermatologist, or a nurse practitioner or physician assistant in a dermatology-focused practice. Most patients (71%) noted a family history of vitiligo (comparable paternal vs maternal). Median body surface area affected by vitiligo was 4.23%, as measured by the self-assessed Vitiligo Extent Scale. In summary, these findings provide a new perspective on the diagnosis journey for patients with vitiligo and highlight the need for accurate, more timely diagnosis

Regional Differences in Glioma: The Role of Pax3 in the Mechanisms and Cellular Origins of Brainstem Glioma

<p>Brain tumors are an incredibly diverse group of neoplasms, as evidenced by their varied locations in the brain, histological characteristics, and genetic alterations. Brain tumor heterogeneity can be potentially explained by distinct oncogenic events or cells-of-origin, or by region-specific intrinsic or extrinsic factors. Brainstem Glioma (BSG) is a particularly deadly brain tumor, afflicting 200-300 children in the United States each year. High-grade BSG (also known as Diffuse Intrinsic Pontine Glioma, DIPG) cannot be surgically removed, and the standard treatment of radiation therapy provides only temporary relief from symptoms. The past 5 years has witnessed a dramatic increase in knowledge regarding the biological basis of this disease along with the realization that BSG is distinct from other more common types of glioma, such as cerebral cortex glioma (CG). It was the goal of this study to investigate the regional differences in gliomas arising in the brainstem versus the cerebral cortex, using mice as a model system, and to begin to understand the contributions of the various possible sources of heterogeneity.</p><p> </p><p>In doing so, we have uncovered region-specific gene expression patterns in these two types of pediatric gliomas that are apparent even when the initiating genetic alterations and cell-of-origin are kept constant. Focusing on the <italic>paired box 3</italic> (Pax3) gene, which is expressed at higher levels in BSG than CG, we have found that Pax3 expression not only characterizes mouse BSGs driven by PDGF signaling, Ink4aARF-loss, p53-loss, and H3.3-K27M expression, but also identifies a novel subset of human BSGs that are associated with <italic>PDGFRA</italic> alterations and wild type <italic>ACVR1</italic> and that commonly harbor <italic>TP53</italic> alterations and the H3.3-K27M mutation. </p><p>As Pax3 plays a pro-tumorigenic role in other types of cancer, we hypothesized that Pax3 expression contributes to the brainstem gliomagenesis process as well. By utilizing mouse models, we found that Pax3 inhibits apoptosis and promotes proliferation of Nestin-expressing brainstem progenitor cells <italic>in vitro</italic> and enhances PDGF-B-driven BSG <italic>in vivo</italic>. Furthermore, we speculate that Pax3 expression may be a marker for Wnt pathway activation in BSG, which is targetable via pharmacologic agents. Indeed, a subset of Wnt inhibitors tested effectively slowed the growth of BSG cells <italic>in vitro</italic>, however cross talk with the Shh pathway might indicate that dual Wnt and Shh inhibition is necessary.</p><p>In addition, the regional expression pattern of Pax3 in gliomas correlates with its expression in normal murine brain development, leading us to hypothesize that Pax3 progenitor cells in the neonatal brainstem can serve as a cell-of-origin for BSG. We discovered that targeting Pax3 progenitors with PDGF-B overexpression and Ink4aARF- or p53-loss induces high-grade BSG that physiologically resemble the human disease. This novel and distinct model of BSG may be utilized in the future for preclinical studies.</p><p>The identification of Pax3 as a regional marker of mouse and human BSG has led to the discovery of a novel subset of the human disease, the identification of a novel oncogene contributing to pathogenesis, and the characterization of a novel cell-of-origin with the potential to give rise to the disease. This information contributes significantly to the current understanding of the mechanisms and cellular origins of BSG, and will hopefully instruct future investigations into how to better treat this disease.</p>Dissertatio

Precision shielding for COVID-19: metrics of assessment and feasibility of deployment

The ability to preferentially protect high-risk groups in COVID-19 is hotly debated. Here, the aim is to present simple metrics of such precision shielding of people at high risk of death after infection by SARS-CoV-2; demonstrate how they can estimated; and examine whether precision shielding was successfully achieved in the first COVID-19 wave. The shielding ratio, S, is defined as the ratio of prevalence of infection among people in a high-risk group versus among people in a low-risk group. The contrasted risk groups examined here are according to age (≥70 vs &lt;70 years), and institutionalised (nursing home) setting. For age-related precision shielding, data were used from large seroprevalence studies with separate prevalence data for elderly versus non-elderly and with at least 1000 assessed people≥70 years old. For setting-related precision shielding, data were analysed from 10 countries where information was available on numbers of nursing home residents, proportion of nursing home residents among COVID-19 deaths and overall population infection fatality rate (IFR). Across 17 seroprevalence studies, the shielding ratio S for elderly versus non-elderly varied between 0.4 (substantial shielding) and 1.6 (substantial inverse protection, that is, low-risk people being protected more than high-risk people). Five studies in the USA all yielded S=0.4–0.8, consistent with some shielding being achieved, while two studies in China yielded S=1.5–1.6, consistent with inverse protection. Assuming 25% IFR among nursing home residents, S values for nursing home residents ranged from 0.07 to 3.1. The best shielding was seen in South Korea (S=0.07) and modest shielding was achieved in Israel, Slovenia, Germany and Denmark. No shielding was achieved in Hungary and Sweden. In Belgium (S=1.9), the UK (S=2.2) and Spain (S=3.1), nursing home residents were far more frequently infected than the rest of the population. In conclusion, the experience from the first wave of COVID-19 suggests that different locations and settings varied markedly in the extent to which they protected high-risk groups. Both effective precision shielding and detrimental inverse protection can happen in real-life circumstances. COVID-19 interventions should seek to achieve maximal precision shielding

Exploring the natural and treatment history of vitiligo: patient and healthcare professional perceptions from the global VALIANT study

BACKGROUND: Vitiligo is a chronic autoimmune disease affecting melanocytes, resulting in depigmentation of skin. Patients with vitiligo often have reduced quality of life and comorbid autoimmune conditions and have reported a lack of available treatments for their vitiligo. OBJECTIVES: The Vitiligo and Life Impact Among International Communities (VALIANT) study is the first global survey to explore the natural history and management of vitiligo from the perspectives of patients and healthcare professionals (HCPs). METHODS: The survey recruited adults (≥18 years) diagnosed with vitiligo and HCPs treating patients with vitiligo via an online panel in 17 countries. Patients were queried regarding clinical characteristics and vitiligo treatment. HCPs were queried regarding diagnosis and management of patients with vitiligo. RESULTS: Included in the analysis were 3541 patients and 1203 HCPs. Nearly half (45.2%) of patients had \u3e5% affected body surface area; 57.1% reported family history. Patients obtained formal diagnosis after a mean (SD) of 2.4 (4.1) years; 44.9% reported previous misdiagnosis. Many patients (56.7%) reported being told that vitiligo could not be treated; 53.9% of HCPs believed patients who never treated their vitiligo were told that vitiligo could not be treated. One-quarter of HCPs (26.3%) did not believe an effective therapy for vitiligo exists; 44.6% of patients reported giving up on finding an effective therapy. Top treatment goals for patients and HCPs, respectively, were reduction/cessation of spread (24.7%/18.5%) and repigmentation (22.5%/37.2%). Patient perception of effective care was similar for treatment by dermatologists (66.9%) and primary care HCPs (67.0%). CONCLUSIONS: Patients with vitiligo and HCPs reported similar treatment goals and expressed frustration with lack of effective therapies. Patients reported high rates of initial misdiagnosis; many ceased seeking healthcare because they perceived that vitiligo could not be treated. Findings highlight the need for earlier diagnosis and improved disease management for vitiligo

Mental Health and Psychosocial Quality-of-Life Burden Among Patients With Vitiligo: Findings From the Global VALIANT Study

IMPORTANCE: Patients with vitiligo often have impaired quality of life (QOL) and experience substantial psychosocial burden. OBJECTIVE: To explore the global association of vitiligo with QOL and mental health from the patient perspective. DESIGN, SETTING, AND PARTICIPANTS: This qualitative study of the cross-sectional population-based Vitiligo and Life Impact Among International Communities (VALIANT) study was conducted from May 6, 2021, to June 21, 2021. Potential participants for this qualitative study were recruited from an online panel in 17 countries. Of 5859 surveyed adults (aged ≥18 years) who reported a vitiligo diagnosis, 3919 (66.9%) completed the survey, and 3541 (60.4%) were included in the analysis. EXPOSURES: Patients were asked questions regarding their emotional well-being, including QOL and mental health. MAIN OUTCOMES AND MEASURES: Reported analyses are descriptive and hypothesis generating. Vitiligo Impact Patient scale (VIPs) scores ranged from 0 to 60, with higher scores indicating more psychosocial burden. RESULTS: The median age of the 3541 patients was 38 years (range, 18-95 years), and 1933 (54.6%) were male; 1602 patients (45.2%) had more than 5% affected body surface area (BSA; Self-Assessment Vitiligo Extent Score assessed), and 1445 patients (40.8%) had Fitzpatrick skin types IV to VI (ie, darker skin). The mean (SD) global short-form VIPs score was 27.3 (15.6) overall; patients from India (mean [SD], 40.2 [14.1]) reported the highest scores (ie, most burden). The QOL burden according to the scale was profound for patients with more than 5% affected BSA (mean [SD] score, 32.6 [14.2]), darker skin (mean [SD] score, 31.2 [15.6]), and lesions on the face (mean [SD] score, 30.0 [14.9]) or hands (mean [SD], 29.2 [15.2]). At least 40% of patients globally reported that vitiligo frequently affected aspects of their daily lives, including choosing clothes to wear (1956 of 3541 [55.2%]). Most patients (2103 of 3541 [59.4%]) reported concealing their vitiligo frequently. More than half of patients (2078 of 3541 [58.7%]) reported diagnosed mental health conditions, including anxiety (1019 of 3541 [28.8%]) and depression (866 of 3541 [24.5%]). The Patient Health Questionnaire-9 depression screener showed that 55.0% of patients (1948 of 3541) had moderate to severe depressive symptoms; the highest rates were in India (271 of 303 [89.4%]) and among patients with more than 5% affected BSA (1154 of 1602 [72.0%]) and darker skin (987 of 1445 [68.3%]). CONCLUSIONS AND RELEVANCE: This qualitative study found that, globally, patients with vitiligo reported being substantially affected in their emotional well-being, daily lives, and psychosocial health; the burden was typically greatest among patients with more than 5% affected BSA, darker skin types, and lesions on the face or hands. Survey findings suggest that patients reported having altered their behavior, expressed clear discontent, and have symptoms consistent with depression, which may be underdiagnosed