Addressing Racial and Ethnic Disparities in Health Care: Using Federal Data to Support Local Programs to Eliminate Disparities

To reduce racial and ethnic disparities in health care, managers, policy makers, and researchers need valid and reliable data on the race and ethnicity of individuals and populations. The federal government is one of the most important sources of such data. In this paper we review the strengths and weaknesses of federal data that pertain to racial and ethnic disparities in health care. We describe recent developments that are likely to influence how these data can be used in the future and discuss how local programs could make use of these data.     

An eighth locus for autosomal dominant retinitis pigmentosa is linked to chromosome 17q

Retinitis pigmentosa is one of the most common causes of severevisual handicap in middle to late life. Prior to this report,seven loci had previously been mapped for the autosomal dominantform of this disorder (adRP). We now report the identificationof a novel adRP locus on chromosome 17q. To map the new locus,we performed linkage analysis with microsatellite markers ina large South African kindred. After exclusion of 13 RP candidategene loci (including rhodopsin and peripherin-RDS), we obtainedsignificant positive lod scores at zero recombination fraction(     

Implementing multiplexed genotyping of non-small-cell lung cancers into routine clinical practice

BackgroundPersonalizing non-small-cell lung cancer (NSCLC) therapy toward oncogene addicted pathway inhibition is effective. Hence, the ability to determine a more comprehensive genotype for each case is becoming essential to optimal cancer care.MethodsWe developed a multiplexed PCR-based assay (SNaPshot) to simultaneously identify >50 mutations in several key NSCLC genes. SNaPshot and FISH for ALK translocations were integrated into routine practice as Clinical Laboratory Improvement Amendments-certified tests. Here, we present analyses of the first 589 patients referred for genotyping.ResultsPathologic prescreening identified 552 (95%) tumors with sufficient tissue for SNaPshot; 51% had ≥1 mutation identified, most commonly in KRAS (24%), EGFR (13%), PIK3CA (4%) and translocations involving ALK (5%). Unanticipated mutations were observed at lower frequencies in IDH and β-catenin. We observed several associations between genotypes and clinical characteristics, including increased PIK3CA mutations in squamous cell cancers. Genotyping distinguished multiple primary cancers from metastatic disease and steered 78 (22%) of the 353 patients with advanced disease toward a genotype-directed targeted therapy.ConclusionsBroad genotyping can be efficiently incorporated into an NSCLC clinic and has great utility in influencing treatment decisions and directing patients toward relevant clinical trials. As more targeted therapies are developed, such multiplexed molecular testing will become a standard part of practice.     

Exploiting cross-priming to generate protective CD8 T-cell immunity rapidly

The number of memory CD8 T cells generated by infection or vaccination correlates strongly with the degree of protection observed in infection and tumor models. Therefore, rapid induction of protective numbers of effector and memory CD8 T cells may be crucial in the case of malignancy, pandemic infection, or bioterrorism. Many studies have shown that amplifying T-cell numbers by prime-boost vaccination is most effective with a substantial time interval between immunizations. In contrast, immunization with peptide-coated mature dendritic cells (DCs) results in a CD8 T-cell response exhibiting accelerated acquisition of memory characteristics, including the ability to respond to booster immunization within days of initial priming. However, personalized DC immunization is too costly, labor intensive, and time-consuming for large-scale vaccination. Here, we demonstrate that in vivo cross-priming with cell-associated antigens or antigen-coated, biodegradable microspheres in the absence of adjuvant quickly generates CD8 T cells that display the phenotype and function of long-term memory populations. Importantly, cross-primed CD8 T cells can respond to booster immunization within days of the initial immunization to generate rapidly large numbers of effector and memory T cells that can protect against bacterial, viral, and parasitic infections, including lethal influenza and malaria-causing Plasmodium infection. Thus, accelerated CD8 T-cell memory after in vivo cross-priming in the absence of adjuvant is generalizable and can be exploited to generate protective immunity rapidly.     

Response to treatment and survival of patients with non-small cell lung cancer undergoing somatic EGFR mutation testing

Somatic mutations in the epidermal growth factor receptor (EGFR) gene are associated with clinical response and prolonged survival in patients with non-small cell lung cancer (NSCLC) treated with EGFR tyrosine kinase inhibitors (TKIs). We began screening patients for somatic EGFR mutations by DNA sequencing as part of clinical care in 2004. We performed a retrospective cohort study of 278 patients with NSCLC referred for EGFR testing over a 10-month period. Tumor samples underwent direct DNA sequence analyses of EGFR exons 18 through 24. We determined the clinical characteristics and EGFR mutation status of the patients and analyzed their response to therapy and survival. EGFR somatic mutations were identified in 68 (24%) of patients. A minimal smoking history was the strongest clinical predictor of harboring a mutation. In multivariable analyses, each pack-year of smoking corresponded to a 5% decreased likelihood of having an EGFR mutation. Among 92 patients with unresectable disease undergoing subsequent systemic therapy, EGFR mutations were associated with an increased response rate to EGFR TKIs (p < .0001) but not chemotherapy. Overall survival was significantly prolonged in EGFR mutation-positive patients (p = .001), with a median survival of 3.1 years compared with 1.6 years in mutation-negative patients, after adjusting for age, gender, and stage at diagnosis. Integrating molecular profiling into clinical care is feasible in NSCLC patients and provides useful clinical information.     

Clinical and Imaging Features of Non–Small-Cell Lung Cancer in Young Patients

BackgroundNon–small-cell lung cancer (NSCLC) in young adult patients is rare, with scarce data available in patients aged < 40 years and even less in those aged < 35 years. Our goal was to determine the presenting symptoms, clinicopathologic characteristics, and imaging features of young patients with NSCLC at time of diagnosis and compare them to those of older adults.Patients and MethodsWe retrospectively analyzed the medical records and imaging of young patients (≤ 40 years old) with NSCLC treated at our institution between 1998 and 2018. Patients < 35 years old were compared to those between 35 and 40 years old. Characteristics of patients ≤ 40 years old were compared to older patients (> 40 years) from publicly available data sets.ResultsWe identified 166 young patients with NSCLC (median age, 36.6 years; range, 18-40 years). Most presented with nonspecific respiratory symptoms and were diagnosed with pneumonia (84/136, 62%). Compared to patients < 35 years old, patients 35-40 years old were more likely to have malignancy detected incidentally (15% vs. 5%, P = .04). Patients < 35 years old were more likely to have central tumors (55% vs. 33%, P = .02) and to have bone (38% vs. 19%, P = .007) and lung (39% vs. 24%, P = .03) metastases. Compared to older patients (> 40 years), young patients were more likely to be never smokers (65.0% vs. 14.7%, P < .001) and to have advanced disease (88% vs. 66%, P < .001).ConclusionYoung patients with NSCLC often present with nonspecific symptoms and have advanced disease at diagnosis, often mimicking other pathologies. Awareness of the clinical presentation and imaging features of NSCLC in young patients may help minimize delays in diagnoses.