Somatic mutations reveal hyperactive Notch signaling and racial disparities in prurigo nodularis.

Prurigo nodularis (PN) is a chronic inflammatory skin disease that disproportionately affects African Americans and is characterized by pruritic skin nodules of unknown etiology. Little is known about genetic alterations in PN pathogenesis, especially relating to somatic events which are often implicated in inflammatory conditions. We thus performed whole-exome sequencing on 54 lesional and nonlesional skin biopsies from 17 PN patients and 10 atopic dermatitis (AD) patients for comparison. Somatic mutational analysis revealed that PN lesional skin harbors pervasive somatic mutations in fibrotic, neurotropic, and cancer-associated genes. Nonsynonymous mutations were most frequent in NOTCH1 and the Notch signaling pathway, a regulator of cellular proliferation and tissue fibrosis, and NOTCH1 mutations were absent in AD. Somatic copy-number analysis, combined with expression data, showed that recurrently deleted and downregulated genes in PN lesional skin are associated with axonal guidance and extension. Follow-up immunofluorescence validation demonstrated increased NOTCH1 expression in PN lesional skin fibroblasts and increased Notch signaling in PN lesional dermis. Finally, multi-center data revealed a significantly increased risk of NOTCH1-associated diseases in PN patients. In characterizing the somatic landscape of PN, we uncover novel insights into its pathophysiology and identify a role for dysregulated Notch signaling in PN.

A cross-sectional analysis of trends in dermatology practice size in the United States from 2012 to 2020.

Physicians are trending towards practice consolidation nationally; however, changes in dermatology practice size remain to be assessed. The objective of this study was to analyze trends in dermatology practice size from 2012 to 2020 using a large-scale Medicare physician database. We performed a retrospective cross-sectional analysis using 2012 and 2020 data obtained from the Physician Compare Database. Responses from dermatologists were analyzed for trends in practice size, with a sub-analysis to examine differences among different regions, gender, and years of experience. The proportion of dermatologists in solo practice decreased from 26.1% in 2012 to 15.6% in 2020 (p < 0.001). Dermatologists were 40% less likely to be practicing in solo practice and 36% more likely to be in a practice with 10 or more members in 2020 (p < 0.001). These findings were consistent among all regions and genders examined. Additionally, in 2020, dermatologists with 30 or more years in practice were 7.5 times more likely to be in solo practice compared to dermatologists with 0-9 years in practice (p < 0.001). There is a trend of dermatologists working for larger practices, which is consistent with a larger nationwide trend of expanding physician practices. This shift in practice settings should be closely monitored to analyze the effect on healthcare efficiency, cost, and delivery.

Health-related quality of life and economic burden of prurigo nodularis.

BACKGROUND: Prurigo nodularis (PN) is an understudied, pruritic inflammatory skin disease. Little is known about the effect of PN on quality of life and its associated economic burden. OBJECTIVE: To quantify the impact of PN on quality of life and its economic implications. METHODS: A cohort study of PN patients (n = 36) was conducted using the Health Utilities Index Mark 3 questionnaire. Control data from US adults (n = 4187) were obtained from the 2002-2003 Joint Canada/United States Survey of Health. Quality-adjusted life year loss and economic costs were estimated by comparing the Health Utilities Index Mark 3 scores of the PN patients with those of the controls. RESULTS: The PN patients had lower overall health performance compared to the controls, (mean ± SE, 0.52 ± 0.06 vs 0.86 ± 0.003, respectively, P < .001). In multivariable regression, PN was found to be associated with worse health performance (coefficient -0.34, 95% CI [-0.46 to -0.23]), most prominent in the pain subdomain (coefficient -0.24, 95% CI [-0.35 to -0.13]). This correlated to an average of 6.5 lifetime quality-adjusted life years lost per patient, translating to an individual lifetime economic burden of $323,292 and a societal burden of $38.8 billion. CONCLUSION: These results demonstrate that PN is associated with significant quality-of-life impairment, similar to the level of other chronic systemic conditions. PN is also associated with a substantial individual economic burden, emphasizing the necessity of research on effective treatment options.

Health-Related QOL and Economic Burden of Chronic Pruritus.

Chronic pruritus (CP) has considerable implications for QOL. However, its impact on health-related QOL and economic burden is not fully characterized. We administered a cross-sectional survey on 132 patients with CP using the Health Utilities Index Mark 3 instrument. Normative data from healthy adults (n = 4,187) were obtained from the Joint Canada/US Survey of Health. Quality-adjusted life-year loss and economic costs were estimated on the basis of Health Utilities Index Mark 3 scores of patients with CP versus controls. Patients with CP had lower overall health performance than the control (0.56 ± 0.03 vs. 0.86 ± 0.003, P < 0.001). In multivariable regression, CP was associated with worse overall health performance (coefficient = -0.30, 95% confidence interval = -0.33 to -0.27), most accentuated in the domains of pain (coefficient = -0.24, confidence interval = -0.28 to -0.21) and emotion (coefficient = -0.11, confidence interval = -0.13 to -0.10). The reduced Health Utilities Index Mark 3 score correlated with 5.5 average lifetime quality-adjusted life-years lost per patient. Using conservative estimates for willingness to pay, the quality-adjusted life-year loss translated to an individual lifetime economic burden of $274,921 and a societal burden of $88.8 billion. CP is associated with significant QOL impairment. The economic burden of CP highlights the necessity for further research into management options.

Predictors of 30-day readmission in Stevens-Johnson syndrome and toxic epidermal necrolysis: A cross-sectional database study.

BACKGROUND: The predictors of readmission in Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) have not been characterized. OBJECTIVE: To determine the variables predictive of 30-day readmission after SJS/TEN hospitalization. METHODS: We performed a cross-sectional study of the 2010-2014 Nationwide Readmissions Database. Bivariate and multivariable logistic regression was used to evaluate associations of patient demographics, comorbidities, and hospital characteristics with readmission. Aggregate and per-readmission costs were calculated. RESULTS: There were 8837 index admissions with SJS/TEN reported; of these, 910 (10.3%) were readmitted, with diagnoses including systemic infection (22.0%), SJS/TEN (20.6%), and cutaneous infection (9.1%). Associated characteristics included age 45 to 64 years (odds ratio [OR], 1.88; 95% confidence interval [CI], 1.43-2.49), Medicaid insurance (OR, 1.83; 95% CI, 1.48-2.27), and nonmetropolitan hospital admission (OR, 1.67; 95% CI, 1.31-2.13). Associated comorbidities included HIV/AIDS (OR, 2.48; 95% CI, 1.63-3.75), collagen vascular disease (OR, 2.38; 95% CI, 1.88-3.00), and metastatic cancer (OR, 2.16; 95% CI, 1.35-3.46). The median per-readmission cost was $10,019 (interquartile range, $4,788-$16,485). LIMITATIONS: The Nationwide Readmissions Database lacks the ability to track the same patient across calendar years. The diagnostic code lacks specificity for hospitalizations <3 days. CONCLUSIONS: Thirty-day readmissions after SJS/TEN hospitalizations are common. Dedicated efforts to identify at-risk patients may improve peridischarge continuity.

Patient characteristics and anesthetic technique are additive but not synergistic predictors of successful motor evoked potential monitoring.

BACKGROUND: Spinal cord monitoring is associated with a significantly lower rate of neurologic deficits after deformity surgery, and has been shown to have predictive value in cervical, thoracic, and lumbar surgery. Lower extremity motor evoked potentials (MEPs) are particularly sensitive to anesthetics and physiologic change, and can be difficult to obtain at baseline. The anesthesiologist is often required to modify the maintenance anesthetic to facilitate signal attainment. Although intuitive, the predictive significance of increasing age, body mass index (BMI), presence of diabetes and/or hypertension, surgical procedure, and anesthetic technique has not been well delineated. METHODS: We conducted a retrospective chart review of the anesthetic records of all patients who underwent spine surgery and MEP monitoring of the lower extremities from August 1, 2001 to December 31, 2005. Patients with preexisting paralysis of the lower extremities were excluded. Univariate analysis was performed to examine the distribution of diabetes, hypertension, anesthesia technique, age, gender, BMI, and surgical procedure. The chi(2) test and the 2-sample t test were used to test associations between MEP status and potential risk factors. Cochran-Armitage test was used to analyze trends in BMI and age by quartile. The effects of diabetes and hypertension, compared with patients with neither, were presented for each anesthetic technique. Bivariate analysis of the data was performed to analyze a potentially synergistic deleterious effect of diabetes, hypertension, and anesthetic technique using the Breslow-Day test for homogeneity of the odds ratios. Logistic regression analysis through stepwise selection was performed to form a model of the data. RESULTS: Two hundred fifty-six charts were reviewed. The univariate analysis showed that diabetes, hypertension, anesthesia technique, age, and BMI were significantly associated with failure to obtain MEP signals. None of the variables were found to have a synergistic effect on MEP signal attainment in the bivariate analysis. Hypertension, diabetes, and anesthetic technique were independent factors for MEP failure and their joint effects were additive not synergistic. CONCLUSIONS: Diabetes, hypertension, and anesthetic technique were the most important patient risk factors associated with failure to obtain lower extremity MEP signals. These results will improve anesthesiologists' ability to tailor anesthetic regimen to patient comorbidity when MEP monitoring is planned.