Single-nucleotide polymorphisms (SNPs) associated with melanoma have been identified though genome-wide association studies. However, the combined impact of these SNPs on melanoma development remains ...unclear, particularly in postmenopausal women who carry a lower melanoma risk.
We examine the contribution of a combined polygenic risk score on melanoma development in postmenopausal women.
Genetic risk scores were calculated using 21 genome-wide association study–significant SNPs. Their combined effect on melanoma development was evaluated in 19,102 postmenopausal white women in the clinical trial and observational study arms of the Women's Health Initiative dataset.
Compared to the tertile of weighted genetic risk score with the lowest genetic risk, the women in the tertile with the highest genetic risk were 1.9 times more likely to develop melanoma (95% confidence interval 1.50-2.42). The incremental change in c-index from adding genetic risk scores to age were 0.075 (95% confidence interval 0.041-0.109) for incident melanoma.
Limitations include a lack of information on nevi count, Fitzpatrick skin type, family history of melanoma, and potential reporting and selection bias in the Women's Health Initiative cohort.
Higher genetic risk is associated with increased melanoma prevalence and incidence in postmenopausal women, but current genetic information may have a limited role in risk prediction when phenotypic information is available.
Adverse drug reactions (ADRs) occur in nearly all patients on chemotherapy, causing morbidity and therapy disruptions. Detection of such ADRs is limited in clinical trials, which are underpowered to ...detect rare events. Early recognition of ADRs in the postmarketing phase could substantially reduce morbidity and decrease societal costs. Internet community health forums provide a mechanism for individuals to discuss real-time health concerns and can enable computational detection of ADRs.
The goal of this study is to identify cutaneous ADR signals in social health networks and compare the frequency and timing of these ADRs to clinical reports in the literature.
We present a natural language processing-based, ADR signal-generation pipeline based on patient posts on Internet social health networks. We identified user posts from the Inspire health forums related to two chemotherapy classes: erlotinib, an epidermal growth factor receptor inhibitor, and nivolumab and pembrolizumab, immune checkpoint inhibitors. We extracted mentions of ADRs from unstructured content of patient posts. We then performed population-level association analyses and time-to-detection analyses.
Our system detected cutaneous ADRs from patient reports with high precision (0.90) and at frequencies comparable to those documented in the literature but an average of 7 months ahead of their literature reporting. Known ADRs were associated with higher proportional reporting ratios compared to negative controls, demonstrating the robustness of our analyses. Our named entity recognition system achieved a 0.738 microaveraged F-measure in detecting ADR entities, not limited to cutaneous ADRs, in health forum posts. Additionally, we discovered the novel ADR of hypohidrosis reported by 23 patients in erlotinib-related posts; this ADR was absent from 15 years of literature on this medication and we recently reported the finding in a clinical oncology journal.
Several hundred million patients report health concerns in social health networks, yet this information is markedly underutilized for pharmacosurveillance. We demonstrated the ability of a natural language processing-based signal-generation pipeline to accurately detect patient reports of ADRs months in advance of literature reporting and the robustness of statistical analyses to validate system detections. Our findings suggest the important contributions that social health network data can play in contributing to more comprehensive and timely pharmacovigilance.
Epidermolysis bullosa describes a group of conditions commonly characterized by fragile skin and blistering of the mucosal membranes. Due to the complex and rare nature of the disease, we sought to ...evaluate the quality and readability of epidermolysis bullosa information available online. Analysis of the top 50 search results on Google demonstrated that information by non‐dermatologists was of a lower reading level and more accessible when compared to information by dermatologists, even though dermatologist written information was more likely to be useful and medically comprehensive. There is an increasing need for dermatologists to provide useful and medically comprehensive EB information that is accessible to patients and patient families.
Histopathologic examination alone can be inadequate for diagnosis of certain melanocytic neoplasms. Recently, a 23-gene expression signature was clinically validated as an ancillary diagnostic test ...to differentiate benign nevi from melanoma. The current study assessed the performance of this test in an independent cohort of melanocytic lesions against clinically proven outcomes.
Archival tissue from primary cutaneous melanomas and melanocytic nevi was obtained from four independent institutions and tested with the gene signature. Cases were selected according to pre-defined clinical outcome measures. Malignant lesions were defined as stage I-III primary cutaneous melanomas that produced distant metastases (metastatic to sites other than proximal sentinel lymph node(s)) following diagnosis of the primary lesion. Melanomas that were metastatic at the time of diagnosis, all re-excisions, and lesions with <10% tumor volume were excluded. Benign lesions were defined as cutaneous melanocytic lesions with no adverse long-term events reported.
Of 239 submitted samples, 182 met inclusion criteria and produced a valid gene expression result. This included 99 primary cutaneous melanomas with proven distant metastases and 83 melanocytic nevi. Median time to melanoma metastasis was 18 months. Median follow-up time for nevi was 74.9 months. The gene expression score differentiated melanoma from nevi with a sensitivity of 93.8% and a specificity of 96.2%.
The results of gene expression testing closely correlate with long-term clinical outcomes of patients with melanocytic neoplasms.
Collectively, this provides strong evidence that the gene signature adds valuable adjunctive information to aid in the accurate diagnosis of melanoma.
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Hidradenitis suppurativa (HS) is a chronic, inflammatory skin disorder characterized by recurrent abscesses in the groin and flexural areas. HS is associated with a wide range of comorbidities that ...complicate the disease course. Although these comorbidities have been well described, it remains unclear how these comorbidities coassociate and whether comorbidity profiles affect disease trajectory. In addition, it is unknown how comorbidity associations are modulated by race and sex. In this comprehensive analysis of 77 million patients in a large US population-based cohort, we examined coassociation patterns among HS comorbidities and identified clinically relevant phenotypic subtypes within HS. We demonstrated that these subtypes not only differed among races, but also influenced clinical outcomes as measured by HS-related emergency department visits and cellulitis. Taken together, our findings provide key insights that elucidate the unique disease trajectories experienced by patients with HS and equip clinicians with a framework for risk stratification and improved targeted care in HS.
Background Across cancers, the decision to pursue genetic testing is influenced more by subjective than objective factors. However, skin cancer, which is more prevalent, visual, and multifactorial ...than many other malignancies, may offer different motivations for pursuing such testing. Objectives The primary objective was to determine factors influencing the decision to receive genetic testing for skin cancer risk. A secondary objective was to assess the impact of priming with health questions on the decision to receive testing. Methods We distributed anonymous online surveys through ResearchMatch.org to assess participant health, demographics, motivations, and interest in pursuing genetic testing for skin cancer risk. Two surveys with identical questions but different question ordering were used to assess the secondary objective. Results We received 3783 responses (64% response rate), and 85.8% desired testing. Subjective factors, including curiosity, perceptions of skin cancer, and anxiety, were the most statistically significant determinants of the decision to pursue testing ( P < .001), followed by history of sun exposure (odds ratio 1.85, P < .01) and history of skin cancer (odds ratio 0.5, P = .01). Age and family history of skin cancer did not influence this decision. Participants increasingly chose testing if first queried about health behaviors ( P < .0001). Limitations The decision to pursue hypothetical testing may differ from in-clinic decision-making. Self-selected, online participants may differ from the general population. Surveys may be subject to response bias. Conclusion The decision to pursue genetic testing for skin cancer is primarily determined by subjective factors, such as anxiety and curiosity. Health factors, including skin cancer history, also influenced decision-making. Priming with consideration of objective health factors can increase the desire to pursue testing.
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