Impact of a Comfortable in our Skin interactive workshop on social media awareness and self-confidence in adolescents.

Social media use contributes to body dissatisfaction and reduced quality of life among adolescents. This study examines the impact of social media use and skin conditions on body image and suggests that a Comfortable in Our Skin (CIOS) pilot community-based workshop may promote healthier body image and social media usage among urban adolescents.

Modeling patient access to therapeutic oxytocin in Zanzibar, Tanzania.

BACKGROUND: Our objective is to estimate the effects of therapeutic oxytocin supply chain factors and social determinants of health on patient access to oxytocin in low-income settings using system dynamics modeling. Postpartum hemorrhage (PPH), a major cause of maternal mortality disproportionately affects women in low and middle income countries (LMICs). The World Health Organization recommends therapeutic oxytocin as the frontline uterotonic for PPH management and prevention. However, lack of access to quality therapeutic oxytocin in Tanzania, and throughout Sub-Saharan Africa, continues to result in a high number of preventable maternal deaths. METHODS: We used publicly available data from Zanzibar and Sub-Saharan Africa, literature review, oxytocin degradation kinetics and previously developed systems dynamics models to understand the barriers in patient access to quality therapeutic oxytocin. RESULTS: The model makes four basic predictions. First, there is a major gap between therapeutic oxytocin procurement and availability. Second, it predicts that at current population increase rates, oxytocin supply will have to be doubled in the next 30 years. Third, supply and storage temperature until 30 °C has minimal effect on oxytocin quality and finally distance of 5 km or less to birthing facility has a small effect on overall access to oxytocin. CONCLUSIONS: The model provides a systems level approach to therapeutic oxytocin access, incorporating supply and procurement, socio-economic factors, as well as storage conditions to understand how women's access to oxytocin over time can be sustained for better health outcomes.

Patient-Reported Outcome Measures for Health-Related Quality of Life in Patients With Psoriasis: A Systematic Review.

Importance: Multiple patient-reported outcome measures (PROMs) for health-related quality of life (HRQL) exist for patients with psoriasis. Evidence for the content validity and other measurement properties of these PROMs is critical to determine which HRQL PROMs could be recommended for use. Objective: To systematically review the validity of HRQL-focused PROMs used in patients with psoriasis. Evidence Review: Using PubMed and Embase, full-text articles published in English or Spanish on development or validation studies for psoriasis-specific, dermatology-specific, or generic HRQL PROMs were included. Development studies included original development studies, even if not studied in psoriasis patients per Consensus-Based Standards for the Selection of Health Measurement Instruments (COSMIN) recommendations. If a study included multiple diagnoses, more than 50% of patients had to have psoriasis or psoriasis-specific subgroup analyses available. Data extraction and analysis followed the COSMIN guidelines. Two independent reviewers extracted and analyzed the data, including PROM characteristics, quality of measurement properties (structural validity, internal consistency, cross-cultural validity, reliability, measurement error, criterion validity, construct validity, and responsiveness), and level of evidence. PROMs were classified into 3 levels of recommendations: (1) PROM recommended for use; (2) PROM requires further validation; and (3) PROM not recommended for use. Findings: Overall, 97 articles were identified for extraction. This included 19 psoriasis-specific, 8 skin-specific, and 6 generic PROMs. According to COSMIN standards, most measures identified received a B recommendation for use, indicating their potential but requiring further validation. Only the Rasch reduced version of the Impact of Psoriasis Questionnaire (IPSO-11 Rasch) received an A recommendation for use given that it had sufficient content validity, structural validity, and internal consistency. Conclusions and Relevance: This study identified a significant lack of information concerning the quality of HRQL measures in psoriasis. This gap in knowledge can be attributed to the fact that traditional measures were developed using validation criteria that differ from the current standards in use. Consequently, additional validation studies in accordance with contemporary standards will be useful in aiding researchers and clinicians in determining the most suitable measure for assessing HRQL in patients with psoriasis.

Melanoma classification and management in the era of molecular medicine.

Melanoma is the most lethal form of skin cancer although surgery is often curative when combined with early screening and prevention. In recurrent or advanced cancer, the emergence of chemotherapy, targeted therapy, and immune checkpoint inhibitors has demonstrated promising clinical outcomes. Such approaches can remarkably halt the progression of disease for many years, although are limited by the acquisition of resistance. The development and approval of combination therapies has further changed the treatment paradigm for certain melanomas. This review focuses on the current state of melanoma epidemiology and recent advancements in melanoma screening, histopathological classification, staged excision (i.e. wide local excision, sentinel lymph node biopsy, and Mohs micrographic surgery), and systemic treatment.

Mendelian Randomization Analysis reveals Inverse Genetic Risks between Skin Cancers and Vitiligo.

Several observational studies have demonstrated a consistent pattern of decreased melanoma risk among patients with vitiligo. More recently, this finding has been supported by a suggested genetic relationship between the two entities, with certain variants significantly associated with an increased risk of melanoma, basal cell carcinoma, and squamous cell carcinoma but a decreased risk of vitiligo. We compared 48 associated variants from a recently published GWAS and identified three variants-located in the TYR, MC1R-DEF8, and RALY-EIF2S2-ASIP-AHCY-ITCH loci- that correlated with an increased risk for melanoma, basal cell carcinoma, and squamous cell carcinoma and a decreased risk for vitiligo. We then used results of skin cancers and vitiligo GWAS to compare the shared genetic properties between these two traits through an unbiased Mendelian randomization analysis. Our results suggest that the inverse genetic relationship between common skin cancers and vitiligo is broader than previously reported owing to the influence of shared genome-wide significant associations.

New Insights into Melanoma Tumor Syndromes.

Melanoma tumor syndromes (MTS) represent an important minority of familial melanoma cases. In these patients, the accumulation of sequence alterations in essential genes may prelude the risk of internal malignancies, in addition to melanoma. Although several host and environmental factors have been implicated in familial melanoma, the exact mechanisms of cancer predisposition-particularly in the context of mixed cancer syndromes-still remain unclear. In this paper, we review new insights into MTS and elucidate recent efforts that guide individualized prognostication and treatment for these diseases in the past quarter century.

Recognition, Staging, and Management of Melanoma.

Melanoma accounts for approximately 1% of all skin cancers but contributes to almost all skin cancer deaths. The developing picture suggests that melanoma phenotypes are driven by epigenetic mechanisms that reflect a complex interplay between genotype and environment. Furthermore, the growing consensus is that current classification standards, notwithstanding pertinent clinical history and appropriate biopsy, fall short of capturing the vast complexity of the disease. This article summarizes the current understanding of the clinical picture of melanoma, with a focus on the tremendous breakthroughs in molecular classification and therapeutics.

Effect of the COVID-19 Pandemic on Delayed Skin Cancer Services.

The COVID-19 pandemic has presented a unique set of challenges to cancer care centers around the world. Diagnostic and treatment delays associated with lockdown periods may be expected to increase the total number of avoidable skin cancer deaths. During this unprecedented time, dermatologists have been pressed to balance early surgical interventions for skin cancer with the risk of viral transmission. This article summarizes evidenced-based recommendations for the surgical management of cutaneous melanoma, keratinocyte cancer, and Merkel cell carcinoma during the COVID-19 pandemic. Additional long-term studies are required to determine the effect of COVID-19 on skin cancer outcomes.

Unsupervised Phenotype-Based Clustering of Clinicopathologic Features in Cutaneous Melanoma.

Pathogenic phenotypes in cutaneous melanoma have been vastly cataloged, although these classifications lack concordance and are confined to either morphological or molecular contexts. In this study, we perform unsupervised k-medoids clustering as a machine learning technique of 2,978 primary cutaneous melanomas at Mass General Brigham and apply this information to elucidate computer-defined subsets within the clinicopathologic domain. We identified five optimally separated clusters of melanoma that occupied two distinct clinicopathologic subspaces: a lower-grade partition associated with common or dysplastic nevi (i.e., nevus-associated melanomas) and a higher-grade partition lacking precursor lesions (i.e., de novo melanomas). Our model found de novo melanomas to be more mitogenic, more ulcerative, and thicker than nevus-associated melanomas, in addition to harboring previously unreported differences in radial and vertical growth phase status. The utilization of mixed clinicopathologic variables, reflective of actual clinical data contained in surgical pathology reports, has the potential to increase the biological relevance of existing melanoma classification schemes and facilitate the discovery of new genomic subtypes.

The Molecular Context of Vulnerability for CDK9 Suppression in Triple Wild-Type Melanoma.

Approximately half of melanoma tumors lack a druggable target and are unresponsive to current targeted therapeutics. One proposed approach for treating these therapeutically orphaned tumors is by targeting transcriptional dependencies (oncogene starvation), whereby survival factors are depleted through inhibition of transcriptional regulators. A drug screen identified a CDK9 inhibitor (SNS-032) to have therapeutic selectivity against wild-type (wt) BRAFwt/NRASwt melanomas compared with BRAFmut/NRASmut mutated melanomas. We then used two strategies to inhibit CDK9 in vitro-a CDK9 degrader (TS-032) and a selective CDK9 kinase inhibitor (NVP-2). At 500 nM, both TS-032 and NVP-2 demonstrated greater suppression of BRAFwt/NRASwt/NF1wt cutaneous and uveal melanomas than mutant melanomas. RNA sequencing analysis of eight melanoma lines with NVP-2 treatment demonstrated that the context of this vulnerability appears to converge on a cell cycle network that includes many transcriptional regulators, such as the E2F family members. The Cancer Genome Atlas human melanoma tumor data further supported a potential oncogenic role for E2F1 and E2F2 in BRAFwt/NRASwt/NF1wt tumors and a direct link to CDK9. Our results suggest that transcriptional blockade through selective targeting of CDK9 is an effective method of suppressing therapeutically orphaned BRAF/NRAS/NF1 wt melanomas.

Predicting resource-dependent maternal health outcomes at a referral hospital in Zanzibar using patient trajectories and mathematical modeling.

Poor intra-facility maternity care is a major contributor to maternal mortality in low- and middle-income countries. Close to 830 women die each day due to preventable maternal complications, partly due to the increasing number of women giving birth in health facilities that are not adequately resourced to manage growing patient populations. Barriers to adequate care during the 'last mile' of healthcare delivery are attributable to deficiencies at multiple levels: education, staff, medication, facilities, and delays in receiving care. Moreover, the scope and multi-scale interdependence of these factors make individual contributions of each challenging to analyze, particularly in settings where basic data registration is often lacking. To address this need, we have designed and implemented a novel systems-level and dynamic mathematical model that simulates the impact of hospital resource allocations on maternal mortality rates at Mnazi Mmoja Hospital (MMH), a referral hospital in Zanzibar, Tanzania. The purpose of this model is to provide a rigorous and flexible tool that enables hospital administrators and public health officials to quantitatively analyze the impact of resource constraints on patient outcomes within the maternity ward, and prioritize key areas for further human or capital investment. Currently, no such tool exists to assist administrators and policy makers with effective resource allocation and planning. This paper describes the structure and construct of the model, provides validation of the assumptions made with anonymized patient data and discusses the predictive capacity of our model. Application of the model to specific resource allocations, maternal treatment plans, and hospital loads at MMH indicates through quantitative results that medicine stocking schedules and staff allocations are key areas that can be addressed to reduce mortality by up to 5-fold. With data-driven evidence provided by the model, hospital staff, administration, and the local ministries of health can enact policy changes and implement targeted interventions to improve maternal health outcomes at MMH. While our model is able to determine specific gaps in resources and health care delivery specifically at MMH, the model should be viewed as an additional tool that may be used by other facilities seeking to analyze and improve maternal health outcomes in resource constrained environments.