Disparities in Tumor Mutational Burden, Immunotherapy Use, and Outcomes Based on Genomic Ancestry in Non-Small-Cell Lung Cancer.

PURPOSE: In patients with advanced non-small-cell lung cancer (aNSCLC), tumor mutational burden (TMB) may vary by genomic ancestry; however, its impact on treatment outcomes is unclear. This retrospective, observational study describes treatment patterns of patients with aNSCLC by genomic ancestry and electronic health record (EHR)-reported race and/or ethnicity and evaluates differences in TMB, cancer immunotherapy (CIT) access, and treatment outcomes across racial and ancestral groups. METHODS: Patients diagnosed with aNSCLC after January 1, 2011, were selected from a real-world deidentified clinicogenomics database and EHR-derived database; continuously enrolled patients were evaluated. Race and/or ethnicity was recorded using variables from the EHR database; genomic ancestry was classified by single-nucleotide polymorphisms on a next-generation sequencing panel. A threshold of 16 mutations per megabase was used to categorize TMB status. RESULTS: Of 59,559 patients in the EHR-derived database and 7,548 patients in the clinicogenomics database, 35,016 (58.8%) and 4,392 (58.2%) were continuously enrolled, respectively. CIT use was similar across EHR-reported race groups, ranging from 34.4% to 37.3% for non-Hispanic Asian and non-Hispanic Black patients, respectively. TMB levels varied significantly across ancestry groups (P < .001); patients of African ancestry had the highest median TMB (8.75 mutations per megabase; interquartile range, 4.35-14.79). In patients who had received CIT, high TMB was associated with improved overall survival compared with low TMB (20.89 v 11.83 months; hazard ratio, 0.60; 95% CI, 0.51 to 0.70) across genomic ancestral groups. CONCLUSION: These results suggest that equitable access to next-generation sequencing may improve aNSCLC outcome disparities in racially and ancestrally diverse populations.

Financial burden of pediatric firearm-related injury admissions in the United States.

Pediatric firearm-related injuries pose a significant public health problem in the United States, yet the associated financial burden has not been well described. This is the first study examining national data on the cost of initial hospitalization for pediatric firearm-related injuries. In this retrospective review, the Healthcare Cost and Utilization Project Kids' Inpatient Database from the years 2003, 2006, 2009, and 2012 was used to identify all patients 18 years of age and under who were admitted with firearm-related injuries. We compared demographic and discharge-level data including injury severity score, hospital length of stay, income quartile, injury intent, and inflation-adjusted hospital costs across age groups (0-5, 6-9, 10-15, 16-18 years). There were approximately 4,753 pediatric firearm-related admissions each year, with a median hospitalization cost of $12,984 per patient. Annual initial hospitalization costs for pediatric firearm injuries were approximately $109 million during the study period. Pediatric firearm-related injuries predominately occured among older teenagers (74%, 16-18 years), males (89%), black individuals (55%), and those from the lowest income quartile (53%). We found significant cost variation based on patient race, income quartile, injury severity score, intent, hospital length of stay, disposition, and hospital region. Inflation-adjusted hospitalization costs have increased significantly over the study period (p < 0.001). Pediatric firearm-related injuries are a large financial burden to the United States healthcare system. There are significant variations in cost based on predictable factors like hospital length of stay and injury severity score; however, there are also substantial discrepancies based on hospital region, patient race, and income quartile that require further investigation.

Three-Dimensional Optical Imaging for Pectus Excavatum Assessment.

BACKGROUND: Corrective surgery for pectus excavatum often relies on the Haller index (HI), derived from chest roentgenograms or computed tomography; however, this exposes children to potentially unnecessary radiation. Our aim was to develop a novel three-dimensional (3D) optical imaging technique to accurately measure chest wall dimensions in a clinically relevant manner. METHODS: Patients with pectus excavatum were imaged using a 3D structured light scanner. Patient characteristics, including height, weight, body mass index, and radiographic HIs (rHI) were recorded. We defined the optical index (OI) as the ratio of the lateral to anterior-posterior measurements obtained from the 3D optical images and compared those to patients' rHIs. Two-thirds of the patients' images were used to develop a predictive model of the rHI, using their OI and biometric data in multilinear regression modeling. The predictive model was applied to the remaining images, and the predicted HIs (pHI) were compared to the rHIs. RESULTS: Optical imaging was performed in 42 patients (ages, 5-35 years) with pectus excavatum; of these, 31 had recent chest roentgenograms, with rHIs ranging from 2.00 to 7.20. The OIs derived from the images correlated closely with rHIs (r = 0.850). Our predictive model, using patients' OI, height, and weight, was able to accurately estimate their rHIs with a median error of 8.11% (interquartile range, 3.5%-17.4%). CONCLUSIONS: 3D optical imaging of patients with pectus excavatum is emerging as an alternative method to assess HIs without the use of ionizing radiation. Additional studies will focus on volumetric quantification of chest wall deformities, using the 3D capabilities of this technology.

Firearm Legislation Stringency and Firearm-Related Fatalities among Children in the US.

BACKGROUND: Firearm-related injuries are the second leading cause of pediatric deaths in the US. We sought to evaluate the effectiveness of both state child access prevention (CAP) laws and gun regulations on pediatric firearm mortality. We hypothesized that states with more stringent firearm legislation had lower pediatric firearm mortality. STUDY DESIGN: We used 2014-2015 firearm mortality data from the Web-Based Injury Statistics Query and Reporting System, 2014 Brady scores (used to quantify stringency of state gun regulations) and CAP laws. State-level covariates were obtained from government sources, including the Bureau of Labor Statistics and the Department of Education. Spearman rank correlations and linear regression were used to determine the relationship between overall pediatric firearm mortality and gun regulations. We also examined the relationship between gun regulations and firearm-related homicides and suicides. RESULTS: Annually, there were approximately 2,715 pediatric firearm fatalities among children; 62.1% were homicides and 31.4% suicides. There was a moderate negative correlation between states' firearm legislation stringency and overall pediatric firearm mortality (ρ = -0.66; p < 0.001), and between CAP laws and firearm suicide rates (ρ = -0.56; p < 0.001). After controlling for poverty, unemployment, substance abuse, and the number of registered firearms, the association between firearm legislation stringency and overall pediatric firearm mortality remained significant (p = 0.04). The association between CAP laws and firearm suicide rate remained significant after controlling for socioeconomic factors, registered firearms, and other firearm legislation (p = 0.04). CONCLUSIONS: Strict gun legislation and CAP laws are associated with fewer pediatric firearm fatalities and firearm suicides, respectively, though no such association was identified with pediatric firearm homicides. Although more studies are needed to determine causality, state-level legislation could play an important role in reducing pediatric firearm-related deaths.

Impact of licensed federal firearm suppliers on firearm-related mortality.

BACKGROUND: Legal firearm sales occur largely through suppliers that have Federal Firearm Licensees (FFLs). Since FFL density might reflect ease-of-access to firearm purchases, we hypothesized that the number of FFL dealers would be associated with firearm-related deaths. We further hypothesized that licensee-type subsets would be associated with differential risks for gun-related deaths. METHODS: We used data from the National Center for Health Statistics National Vital Statistics System (2008-2014) and national data on Federal Firearms Licensees for 2014. Correlation analysis and linear regression analysis were performed to determine the relationship between different licensee types and firearm-related deaths. We controlled for population, number of statewide registered firearms, and the density of other types of FFLs. RESULTS: We identified a total of 65,297 FFLs. There was a moderate correlation (R = 0.53, ρ = 0.48) between total FFL density and firearm-related death rates. Further analysis by type of firearm-related death showed a strong correlation (R = 0.81, ρ = 0.76) between total FFL density and firearm-related suicide rates. No correlation was found between total FFL density and firearm-related homicide rate. Among individual FFL types, FFL02 (firearm dealing pawnshop) density was the only FFL-type found to be correlated with firearm-related death rates. We found a strong correlation between FFL02 density and overall firearm-related death rate (R = 0.69, ρ = 0.78) and firearm-related suicide rate (R = 0.72, ρ = 0.78). Linear regression analysis showed that even while controlling for number of registered firearms and population, the number of firearm-dealing pawnshops remained significantly associated with overall firearm-related deaths and firearm-related suicides. CONCLUSION: Access to legally distributed firearms is associated with firearm-related death rates, particularly firearm-related suicides. Specifically, firearm-dealing pawnshops were associated with suicide-related deaths. These findings suggest that deeper exploration of legal firearm access and firearm-related injuries would benefit discussion of preventative measures. LEVEL OF EVIDENCE: Therapeutic, Level V.

Intelligent Word Embeddings of Free-Text Radiology Reports.

Radiology reports are a rich resource for advancing deep learning applications in medicine by leveraging the large volume of data continuously being updated, integrated, and shared. However, there are significant challenges as well, largely due to the ambiguity and subtlety of natural language. We propose a hybrid strategy that combines semantic-dictionary mapping and word2vec modeling for creating dense vector embeddings of free-text radiology reports. Our method leverages the benefits of both semantic-dictionary mapping as well as unsupervised learning. Using the vector representation, we automatically classify the radiology reports into three classes denoting confidence in the diagnosis of intracranial hemorrhage by the interpreting radiologist. We performed experiments with varying hyperparameter settings of the word embeddings and a range of different classifiers. Best performance achieved was a weighted precision of 88% and weighted recall of 90%. Our work offers the potential to leverage unstructured electronic health record data by allowing direct analysis of narrative clinical notes.