Addressing Sex Disparities in Lung Cancer Screening Eligibility: USPSTF vs PLCOm2012 Criteria.

BACKGROUND: Lung cancer is the leading cause of cancer death in women in the United States. Prospective randomized lung screening trials suggest a greater lung cancer mortality benefit from screening women compared with men. RESEARCH QUESTION: Do the United States Preventative Services Task Force (USPSTF) lung screening guidelines that are based solely on age and smoking history contribute to sex disparities in eligibility, and if so, does the use of the PLCOm2012 risk prediction model that is based on 11 predictors of lung cancer reduce sex disparities? STUDY DESIGN AND METHODS: This retrospective analysis of 883 lung cancer cases in the Chicago Race Eligibility for Screening Cohort (CREST) determined the sensitivity of USPSTF vs PLCOm2012 eligibility criteria, stratified according to sex. For comparisons vs the USPSTF 2013 and the recently published USPSTF 2021 (released March 9, 2021) eligibility criteria, the PLCOm2012 model was used with risk thresholds of ≥ 1.7%/6 years (6y) and ≥ 1.0%/6y, respectively. RESULTS: The sensitivities for screening by the USPSTF 2013 were 46.7% for women and 64.6% for men (P = .003) and by the USPSTF 2021 were 56.8% and 71.8%, respectively (P = .02). In contrast, the PLCOm2012 ≥ 1.7%/6y sensitivities were 64.6% and 70.4%, and the PLCOm2012 ≥ 1.0%/6y sensitivities were 77.4% and 82.4%. The PLCOm2012 differences in sensitivity using ≥ 1.7%/6y and ≥ 1.0%/6y thresholds between women and men were nonsignificant (both, P = .07). Compared with men, women were more likely to be ineligible according to the USPSTF 2021 criteria because their smoking exposures were < 20 pack-years (22.8% vs 14.8%; ORWomen vs Men, 1.70; 95% CI, 1.19-2.44; P = .002), and 27% of these ineligible women were eligible according to the PLCOm2012 ≥ 1.0%/6y criteria. INTERPRETATION: Although the USPSTF 2021 eligibility criteria are more sensitive than the USPSTF 2013 guidelines, sex disparities in eligibility remain. Adding the PLCOm2012 risk prediction model to the USPSTF guidelines would improve sensitivity and attenuate sex disparities.

Improving Referrals to Preschool Special Education in Pediatric Primary Care.

INTRODUCTION: The American Academy of Pediatrics created evidence-based guidelines that encourage early identification and referral for children with developmental delays. Although pediatric primary care providers are poised to link 3-to-5-year-old children to school-based services, there are gaps in making referrals. METHOD: Educational dissemination of streamlined referral packets was introduced. Knowledge and perceived confidence were measured following an educational presentation. Retrospective chart reviews compared referral rates to preschool special education services when developmental delays were identified. RESULTS: Mean pretest to posttest knowledge and perceived confidence to refer children to preschool special education increased following education. Referral rates for 3-5 years-old by pediatric primary care providers doubled during the initial 8-week implementation period and remained constant 9 months later. DISCUSSION: Educational dissemination of a streamlined referral process in pediatric primary care is a sustainable approach that ensures preschool-aged children with developmental delays receive timely referrals for further school-based evaluations and interventions.

Deletion of the K1L Gene Results in a Vaccinia Virus That Is Less Pathogenic Due to Muted Innate Immune Responses, yet Still Elicits Protective Immunity.

All viruses strategically alter the antiviral immune response to their benefit. The vaccinia virus (VACV) K1 protein has multiple immunomodulatory effects in tissue culture models of infection, including NF-κB antagonism. However, the effect of K1 during animal infection is poorly understood. We determined that a K1L-less vaccinia virus (vΔK1L) was less pathogenic than wild-type VACV in intranasal and intradermal models of infection. Decreased pathogenicity was correlated with diminished virus replication in intranasally infected mice. However, in intradermally inoculated ears, vΔK1L replicated to levels nearly identical to those of VACV, implying that the decreased immune response to vΔK1L infection, not virus replication, dictated lesion size. Several lines of evidence support this theory. First, vΔK1L induced slightly less edema than vK1L, as revealed by histopathology and noninvasive quantitative ultrasound technology (QUS). Second, infiltrating immune cell populations were decreased in vΔK1L-infected ears. Third, cytokine and chemokine gene expression was decreased in vΔK1L-infected ears. While these results identified the biological basis for smaller lesions, they remained puzzling; because K1 antagonizes NF-κB in vitro, antiviral gene expression was expected to be higher during vΔK1L infection. Despite these diminished innate immune responses, vΔK1L vaccination induced a protective VACV-specific CD8+ T cell response and protected against a lethal VACV challenge. Thus, vΔK1L is the first vaccinia virus construct reported that caused a muted innate immune gene expression profile and decreased immune cell infiltration in an intradermal model of infection yet still elicited protective immunity.IMPORTANCE The vaccinia virus (VACV) K1 protein inhibits NF-κB activation among its other antagonistic functions. A virus lacking K1 (vΔK1L) was predicted to be less pathogenic because it would trigger a more robust antiviral immune response than VACV. Indeed, vΔK1L was less pathogenic in intradermally infected mouse ear pinnae. However, vΔK1L infection unexpectedly elicited dramatically reduced infiltration of innate immune cells into ears. This was likely due to decreased expression of cytokine and chemokine genes in vΔK1L-infected ears. As such, our finding contradicted observations from cell culture systems. Interestingly, vΔK1L conferred protective immunity against lethal VACV challenge. This suggests that the muted immune response triggered during vΔK1L infection remained sufficient to mount an effective protective response. Our results highlight the complexity and unpredictable nature of virus-host interactions, a relationship that must be understood to better comprehend virus pathogenesis or to manipulate viruses for use as vaccines.