Eligibility for cervical cancer screening exit: Comparison of a national and safety net cohort.

OBJECTIVE: To determine eligibility for discontinuation of cervical cancer screening. METHODS: Women aged 64 with employer-sponsored insurance enrolled in a national database between 2016 and 2018, and those aged 64-66 receiving primary care at a safety net health center in 2019 were included. Patients were evaluated for screening exit eligibility by current guidelines: no evidence of cervical cancer or HIV-positive status and no evidence of cervical precancer in the past 25 years, and had evidence of either hysterectomy with removal of the cervix or evidence of fulfilling screening exit criteria, defined as two HPV screening tests or HPV plus Pap co-tests or three Pap tests within the past 10 years without evidence of an abnormal result. RESULTS: Of the 590,901 women in the national claims database, 131,059 (22.2%) were eligible to exit due to hysterectomy (1.6%) or negative screening (20.6%). Of the 1544 women from the safety net health center, 528 (34.2%) were eligible to exit due to hysterectomy (9.3%) or negative screening (24.9%). Most women did not have sufficient data available to fulfill exit criteria: 382,509 (64.7%) in the national database and 875 (56.7%) in the safety net hospital system. Even among women with 10 years of insurance claims data, only 41.5% qualified to discontinue screening. CONCLUSIONS: Examining insurance claims in a national database and electronic medical records at a safety net institution led to remarkably similar findings: two thirds of women fail to qualify for screening exit. Additional steps to ensure eligibility prior to screening exit may be necessary to decrease preventable cervical cancers among women aged >65. CLINICAL TRIAL REGISTRATION: N/A.

CYP2D6 Allelic Variants *34, *17-2, *17-3, and *53 and a Thr309Ala Mutant Display Altered Kinetics and NADPH Coupling in Metabolism of Bufuralol and Dextromethorphan and Altered Susceptibility to Inactivation by SCH 66712.

Metabolic phenotype can be affected by multiple factors, including allelic variation and interactions with inhibitors. Human CYP2D6 is responsible for approximately 20% of cytochrome P450-mediated drug metabolism but consists of more than 100 known variants; several variants are commonly found in the population, whereas others are quite rare. Four CYP2D6 allelic variants-three with a series of mutations distal to the active site (*34, *17-2, *17-3) and one ultra-metabolizer with mutations near the active site (*53), along with reference *1 and an active site mutant of *1 (Thr309Ala)-were expressed, purified, and studied for interactions with the typical substrates dextromethorphan and bufuralol and the inactivator SCH 66712. We found that *34, *17-2, and *17-3 displayed reduced enzyme activity and NADPH coupling while producing the same metabolites as *1, suggesting a possible role for Arg296 in NADPH coupling. A higher-activity variant, *53, displayed similar NADPH coupling to *1 but was less susceptible to inactivation by SCH 66712. The Thr309Ala mutant showed similar activity to that of *1 but with greatly reduced NADPH coupling. Overall, these results suggest that kinetic and metabolic analysis of individual CYP2D6 variants is required to understand their possible contributions to variable drug response and the complexity of personalized medicine.

Socially Responsible Surgery: Building Recognition and Coalition.

IMPORTANCE: Socially responsible surgery (SRS) integrates surgery and public health, providing a framework for research, advocacy, education, and clinical practice to address the social barriers of health that decrease surgical access and worsen surgical outcomes in underserved patient populations. These patients face disparities in both health and in health care, which can be effectively addressed by surgeons in collaboration with allied health professionals. OBJECTIVE: We reviewed the current state of surgical access and outcomes of underserved populations in American rural communities, American urban communities, and in low- and middle-income countries. EVIDENCE REVIEW: We searched PubMed using standardized search terms and reviewed the reference lists of highly relevant articles. We reviewed the reports of two recent global surgery commissions. CONCLUSION: There is an opportunity for scholarship in rural surgery, urban surgery, and global surgery to be unified under the concept of SRS. The burden of surgical disease and the challenges to management demonstrate that achieving optimal health outcomes requires more than excellent perioperative care. Surgeons can and should regularly address the social determinants of health experienced by their patients. Formalized research and training opportunities are needed to meet the growing enthusiasm among surgeons and trainees to develop their practice as socially responsible surgeons.