Exploratory Analysis of Concordance Between Clinician-Collected and Self-Sampled Human Papillomavirus Tests in a Small Cohort of Average- and High-Risk Patients.

Objectives: Cervical cancer screening rates have stagnated, but self-sampling modalities have the potential to increase uptake. This study compares the test characteristics of self-sampled high-risk human papillomavirus (hrHPV) tests with clinician-collected hrHPV tests in average-risk (i.e., undergoing routine screening) and high-risk patients (i.e., receiving follow-up after abnormal screening results). Methods: In this cross-sectional study, a relatively small cohort of average-risk (n = 35) and high-risk (n = 12) participants completed both clinician-collected and self-sampled hrHPV testing, along with a brief phone survey. We assessed hrHPV positivity, concordance, positive predictive value (PPV), negative predictive value (NPV), sensitivity, and specificity across both methods (for types 16, 18, or other hrHPV). We also explored the relationship between test concordance and sociodemographic/behavioral factors. Results: Among average-risk participants, hrHPV positivity was 6% for both test methods (i.e., hrHPV-positive cases: n = 2), resulting in reported concordance, PPV, NPV, sensitivity, and specificity of 100%. Among high-risk participants, hrHPV positivity was 100% for clinician-collected tests but only 67% for self-sampled tests, showing varied concordance and sensitivity. Concordance was not associated with sociodemographic or behavioral factors. Conclusions: Self-sampled hrHPV testing demonstrated high accuracy for average-risk patients in this exploratory study. However, its performance was less consistent in high-risk patients who had already received an abnormal screening result, which could be attributed to spontaneous viral clearance over time. The limited number of participants, particularly HPV-positive cases, suggests caution in interpreting these results. Further research with larger cohorts is necessary to validate these findings and to explore the integration of self-sampled hrHPV testing into routine clinical care, particularly for patients with a history of cervical abnormalities. Clinical Trial Registration: NCT04591977, NCT04585243.

Self-sampling tools to increase cancer screening among underserved patients: a pilot randomized controlled trial.

BACKGROUND: Screening can reduce cancer mortality, but uptake is suboptimal and characterized by disparities. Home-based self-sampling can facilitate screening for colorectal cancer (with stool tests, eg, fecal immunochemical tests) and for cervical cancer (with self-collected human papillomavirus tests), especially among patients who face barriers to accessing health care. Additional data are needed on feasibility and potential effects of self-sampling tools for cancer screening among underserved patients. METHODS: We conducted a pilot randomized controlled trial with patients (female, ages 50-65 years, out of date with colorectal and cervical cancer screening) recruited from federally qualified health centers in rural and racially segregated counties in Pennsylvania. Participants in the standard-of-care arm (n = 24) received screening reminder letters. Participants in the self-sampling arm (n = 24) received self-sampling tools for fecal immunochemical tests and human papillomavirus testing. We assessed uptake of screening (10-week follow-up), self-sampling screening outcomes, and psychosocial variables. Analyses used Fisher exact tests to assess the effect of study arm on outcomes. RESULTS: Cancer screening was higher in the self-sampling arm than the standard-of-care arm (colorectal: 75% vs 13%, respectively, odds ratio = 31.32, 95% confidence interval = 5.20 to 289.33; cervical: 79% vs 8%, odds ratio = 72.03, 95% confidence interval = 9.15 to 1141.41). Among participants who returned the self-sampling tools, the prevalence of abnormal findings was 24% for colorectal and 18% for cervical cancer screening. Cancer screening knowledge was positively associated with uptake (P < .05). CONCLUSIONS: Self-sampling tools can increase colorectal and cervical cancer screening among unscreened, underserved patients. Increasing the use of self-sampling tools can improve primary care and cancer detection among underserved patients. CLINICAL TRIALS REGISTRATION NUMBER: STUDY00015480.

Utilization of Mammography During the Last Year of Life Among Older Breast Cancer Survivors.

Background: Mammography is generally recommended for breast cancer survivors. However, discussion is ongoing about stopping surveillance mammography when life expectancy is <5-10 years as the benefit of screening might be diminished toward the end of life. The utilization pattern of mammography in the last year of life among this population has not been well studied. Methods: We identified 58,736 females diagnosed with breast cancer between January 2002 and December 2015, who died at the age of at least 67, from the SEER-Medicare database. We examined the utilization patterns of mammography during their last year of life and investigated factors associated with the use of mammography at the end of life using a multivariable logistic regression model. Results: Overall, 28.5% of the patients received mammography during the last year of life. Multivariable logistic regression showed that older age (OR = 0.31, 95% CI = 0.29-0.34, p < 0.001 for 95 vs. 85 years old), more advanced cancer stage (OR = 0.22, 95% CI = 0.20-0.24 p < 0.001 for distant vs. localized disease), and higher comorbidity score (OR = 0.92, 95% CI = 0.91-0.93, p < 0.001 for every 1-point increase) were associated with less mammography use. Age was nonlinearly associated with mammography use, with a steady proportion of patients receiving a mammography until approximately age 80 and then a sharp decrease thereafter. Conclusion: This population-based study found that a sizable proportion of older breast cancer survivors received mammography during the last year of life.

Multilevel Associations with Cancer Screening Among Women in Rural, Segregated Communities Within the Northeastern USA: a Mixed-Methods Study.

We recruited women (primarily non-Hispanic White) from 14 rural, segregated counties in a Northeastern US state for an explanatory sequential study: 100 women (ages 50-65 years) completed a survey, and 16 women participated in focus groups. We sought to identify personal (e.g., healthcare mistrust) and environmental (e.g., travel time to healthcare providers) factors related to colorectal and cervical cancer screening. Quantitatively, 89% of participants were up-to-date for cervical screening, and 65% for colorectal screening. Factors interacted such that compounding barriers were associated with lower odds of screening (e.g., insurance status and healthcare mistrust: interaction p = .02 for cervical; interaction p = .05 for colorectal). Qualitatively, three themes emerged regarding barriers to screening: privacy concerns, logistical barriers, and lack of trust in adequacy of healthcare services. While cancer screening was common in rural, segregated counties, women who reported both environmental and personal barriers to screening had lower uptake. Future interventions to promote screening can target these barriers.

Changes in Serum, Red Blood Cell, and Colonic Fatty Acids in a Personalized Omega-3 Fatty Acid Supplementation Trial.

This study evaluated changes in fatty acids from sera, red blood cells, and colonic biopsies from a phase Ib clinical trial of personalized ω-3 fatty acid dosing in 47 healthy volunteers. The trial aimed to reduce colonic prostaglandin E2 (PGE2), a pro-inflammatory product of arachidonic acid (AA) oxidation. The personalized doses ranged 2-10 grams/day (54% eicosapentaenoic acid, EPA, 24% other ω-3 fatty acids). In colon, increases in ω-3 highly unsaturated fatty acids (HUFA) and EPA:AA ratios each were correlated with decreases in PGE2. Changes in either colonic EPA:AA ratios or ω-3 HUFA were significantly correlated with changes in the same fatty acid measures in red blood cells or serum. The only blood-based measure significantly correlated with changes in colonic PGE2 was change in red blood cell ω-3 HUFA (ρ = -0.39), and the increase in red blood cell ω-3 HUFA was significantly greater in participants who had at least a median reduction in colonic PGE2 vs. those who did not. In summary, fatty acid changes in blood did reflect fatty acid changes in the colon, but additional factors will be needed for optimizing dosing models that seek to predict the anti-inflammatory effects of ω-3 fatty acids on the colon.

Disparities in Cancer Screening: The Role of County-Level Metropolitan Status and Racial Residential Segregation.

Mortality from cervical and colorectal cancers can be reduced through routine screening, which can often be accessed through primary care. However, uptake of screening in the US remains suboptimal, with disparities observed across geographic characteristics, such as metropolitan status or level of racial residential segregation. Little is known about the interaction of metropolitan status and segregation in their relationship with cancer screening. We conducted a quantitative survey of 474 women aged 45-65 in central Pennsylvania. The survey collected county-level characteristics and participant-level demographics, beliefs, cancer screening barriers, and cervical and colorectal cancer screening. We used bivariate and multivariable logistic regression to analyze relationships between metropolitan status and segregation with screening. For cervical cancer screening, 82.8% of participants were up-to-date, which did not differ by county type in the final analysis. Higher healthcare trust, higher cancer fatalism, and reporting cost as a barrier were associated with cervical cancer screening. For colorectal cancer screening, 55.4% of participants were up-to-date, which differed by county type. In metropolitan counties, segregation was not associated with colorectal cancer screening, but in non-metropolitan counties, segregation was associated with greater colorectal cancer screening. The relationship between metropolitan status and being up-to-date with colorectal, but not cervical, cancer screening varied by segregation. Other important beliefs and barriers to screening varied by county type. This research can guide future cancer screening interventions in primary care settings in underserved communities.

Association Between Dense Breast Legislation and Cancer Stage at Diagnosis.

INTRODUCTION: Many states have mandated breast density notification and insurance coverage for additional screening; yet, the association between such legislation and stage of diagnosis for breast cancer is unclear. This study investigates this association and examines the differential impacts among different age and race/ethnicity subgroups. METHODS: The Surveillance, Epidemiology, and End Results database was queried to identify patients with breast cancer aged 40-74 years diagnosed between 2005 and 2016. Using a difference-in-differences multinomial logistic model, the odds of being diagnosed at different stages of cancer relative to the localized stage depending on legislation and individual characteristics were examined. Analyses were conducted in 2020-2021. RESULTS: The study included 689,641 cases. Overall, the impact of notification legislation was not significant, whereas insurance coverage legislation was associated with 6% lower odds (OR=0.94, 95% CI=0.91, 0.96) of being diagnosed at the regional stage. The association between insurance coverage legislation and stage of diagnosis was even stronger among women aged 40-49 years, with 11% lower odds (OR=0.89, 95% CI=0.82, 0.96) of being diagnosed at the regional stage and 12% lower odds (OR=0.88, 95% CI=0.81, 0.96) of being diagnosed at the distant stage. Hispanic women benefited from notification laws, with 11% lower odds (OR=0.89, 95% CI=0.82, 0.97) of being diagnosed at distant stage. Neither notification nor supplemental screening insurance coverage legislation showed a substantial impact on Black women. CONCLUSIONS: The findings imply that improving insurance coverage is more important than being notified overall. Raising awareness is important among Hispanic women; improving communication about dense breasts and access to screening might be more important than legislation among Black women.

Predictors of Human Papillomavirus Seropositivity in Appalachian Women Aged 18 to 26 Years.

BACKGROUND: Key informants of the Appalachian community questioned whether their unique environmental stressors would alter their immune response to human papillomavirus (HPV) infections. The primary aim of this study is to determine predictors of HPV seroprevalence to at least 1 of the 4 vaccine-related HPV types before vaccination using a psychoneuroimmunologic model in Appalachian women. METHOD: Women aged 18 to 26 years (n = 185) who had not received HPV vaccination provided cervical HPV DNA and blood samples. Human papillomavirus DNA was identified through Hybrid Capture 2 assay and then genotyped for HPV types 6, 11, 16, and 18 by Roche Linear Array. Competitive Luminex Immunoassay measured the type-specific antibodies to HPV types 6, 11, 16, and 18 in milli-Merck units per milliliter. Nine psychoneuroimmunology scales measuring attributes of stress were self-completed. RESULTS: Human papillomavirus DNA was detected in 50% (92/183) of participants, with only 14% (26/183) positive for HPV-6/11/16/18 DNA. Seropositivity for at least one anti-HPV-6/11/16 or 18, on the other hand, was present in 35% (64/183) of women, with only 10% (19/183) concomitantly infected and seropositive for the vaccine-related types. The Perceived Stress Scale was not a strong predictor of HPV seropositivity. CONCLUSIONS: Both HPV infection and vaccine-related HPV type seropositivity is common among Appalachian women aged 18 to 26 years. The anticipated effect of environmental stressors on HPV seropositivity was not seen when multiple predictors were considered.

Knowledge, Perceptions, and Preferred Information Sources Related to COVID-19 Among Central Pennsylvania Adults Early in the Pandemic: A Mixed Methods Cross-Sectional Survey.

PURPOSE: To explore public knowledge, understanding of public health recommendations, perceptions, and trust in information sources related to COVID-19. METHODS: A cross-sectional survey of central Pennsylvanian adults evaluated self-reported knowledge, and a convergent, mixed methods design was used to assess beliefs about recommendations, intended behaviors, perceptions, and concerns related to infectious disease risk, and trust of information sources. RESULTS: The survey was completed by 5,948 adults. The estimated probability of correct response for the basic knowledge score, weighted with confidence, was 0.79 (95% CI, 0.79-0.80). Knowledge was significantly higher in patients with higher education and nonminority race. While the majority of respondents reported that they believed following CDC recommendations would decrease the spread of COVID-19 in their community and intended to adhere to them, only 65.2% rated social isolation with the highest level of belief and adherence. The most trusted information source was federal public health websites (42.8%). Qualitative responses aligned with quantitative data and described concerns about illness, epidemiologic issues, economic and societal disruptions, and distrust of the executive branch's messaging. The survey was limited by a lack of minority representation, potential selection bias, and evolving COVID-19 information that may impact generalizability and interpretability. CONCLUSIONS: Knowledge about COVID-19 and intended adherence to behavioral recommendations were high. There was substantial distrust of the executive branch of the federal government, however, and concern about mixed messaging and information overload. These findings highlight the importance of consistent messaging from trusted sources that reaches diverse groups.

Pharmacogenomic testing for mental health (Part I): documenting early adopter perceptions of use for eight scenarios.

Aim: We sought to understand how early adopters used pharmacogenomic (PGx) testing for treating depression and attention deficient hyperactivity disorder (ADHD). Patients & methods: We conducted a phone survey with prescribers who had previously ordered an Informed PGx (Progenity, Inc., MI, USA) test. Results: We identified 1037 prescribers in our sampling period. Respondents (n = 64) were predominantly female (61.5%) and in pediatrics (n = 42; 64.6%). PGx testing was used for multiple scenarios (mean 3.3 ± 1.6); the most common was after no response to medication was observed (80%; 51/64). Most respondents state that test results typically reveal an altered metabolizer status. Conclusion: PGx test results ordered by early adopters often reveal altered metabolizers which leads them to change the depression/ADHD medication regimen. Future work should evaluate the clinical utility of PGx testing for depression/ADHD treatment.

Examining Older Adults' Attitudes and Perceptions of Cancer Screening and Overscreening: A Qualitative Study.

INTRODUCTION/OBJECTIVES: Screening guidelines for breast, cervical, and colorectal cancer (CRC) are less clear for older adults due to the potential harms that may result from screening. Understanding older adults' attitudes and perceptions, especially racial/ethnic minority and underserved adults, of cancer screening can help health care providers determine how best to communicate with older adults about cancer screening and screening cessation. The objective of this study was to determine how older adults primarily from minority/underserved backgrounds perceive cancer screening and overscreening. METHODS: Four focus groups (n = 39) were conducted with adults (>=65 years of age) in 3 community settings in south-central Pennsylvania. Two focus groups were conducted in Spanish and translated to English upon transcription. Focus group data was managed and analyzed using QSR NVivo 12. Inductive thematic analysis was used to analyze the data where themes emerged following the coding process. RESULTS: The focus group participants had an average age of 74 years and were primarily female (74%) and Hispanic (69%), with 69% reporting having less than a high school degree. Four key themes were identified from the focus groups: (1) importance of tailored and targeted education/information; (2) impact of physician/patient communication; (3) impact of barriers and facilitators to screening on cancer screening cessation; and (4) awareness of importance of screening. Participants were more likely to be agreeable to screening cessation if they received specific information regarding their health status and previous medical history from their physician as to why screening should be stopped and told by their physician that the screening decision is up to them. CONCLUSIONS: Older adults prefer individualized information from their physician in order to justify screening cessation but are against incorporating life expectancy into the discussion. Future research should focus on developing interventions to test the effectiveness of culturally tailored screening cessation messages for older adults.

Public Intent to Comply with COVID-19 Public Health Recommendations.

Stay-at-home orders have been an essential component of coronavirus 2019 (COVID-19) management in the United States. As states start lifting these mandates to reopen the economy, voluntary public compliance with public health recommendations may significantly influence the extent of resurgence in COVID-19 infection rates. Population-level risk from reopening may therefore be predicted from public intent to comply with public health recommendations. We are conducting a global, convergent design mixed-methods survey on public knowledge, perceptions, preferred health information sources, and understanding of and intent to comply with public health recommendations. With over 9,000 completed surveys from every US state and over 70 countries worldwide, to our knowledge this is the largest pandemic messaging study to date. Although the study is still ongoing, we have conducted an analysis of 5,005 US surveys completed from April 9-15, 2020 on public intent to comply with public health recommendations and offer insights on the COVID-19 pandemic-related risk of reopening. We found marked regional differences in intent to follow key public health recommendations. Regional efforts are urgently needed to influence public behavior changes to decrease the risk of reopening, particularly in higher-risk areas with low public intent to comply with preventive health recommendations. [HLRP: Health Literacy Research and Practice. 2020;4(3):e160-e165.].

An Adaptive Bayesian Design for Personalized Dosing in a Cancer Prevention Trial.

INTRODUCTION: In biomarker-driven clinical trials, translational strategies typically involve moving findings from animal experiments to human trials. Typically, the translation is static, using a fixed model derived from animal experiments for the duration of the trial. Bayesian designs, capable of incorporating information external to the experiment, provide a dynamic translational strategy. This article demonstrates an example of such a dynamic Bayesian strategy in a clinical trial. METHODS: This study explored the effect of a personalized dose of fish oil for reducing prostaglandin E2, an inflammatory marker linked to colorectal cancer. A Bayesian design was implemented for the dose-finding algorithm that adaptively updated a dose-response model derived from a previously completed animal study during the clinical trial. In the initial stages of the trial, the dose-response model parameters were estimated from the rodent data. The model was updated following a Bayesian algorithm after data on every 10‒15 subjects were obtained until the model stabilized. Subjects were enrolled in the study between 2013 and 2015, and the data analysis was carried out in 2016. RESULTS: The 3 dosing models were used for groups of 16, 15, and 15 subjects. The mean target dose significantly decreased from 6.63 g/day (Model 1) to 4.06 g/day (Model 3) (p=0.001). Compared with the static strategy of dosing with a single model, the dynamic modeling reduced the dose significantly by about 1.38 g/day on average. CONCLUSIONS: A Bayesian design was effective in adaptively revising the dosing algorithm, resulting in a lower pill burden. TRIAL REGISTRATION: This study is registered at www.clinicaltrials.gov NCT01860352.

Japanese Women's Concerns and Satisfaction With Pregnancy Care in the United States.

Immigrant women report a high level of stress during pregnancy due to language barriers, cultural differences, and differences in the standard of prenatal care. In this study, we evaluated the level of concern Japanese women in the United States feel during pregnancy and their level of satisfaction with their care. This data can be used to modify prenatal care programs and education to address these concerns. Data collected from 96 women showed there was a high level of prenatal concern regarding their baby's health, pain control, the short length of hospitalization after birth, and the lack of breastfeeding support. Despite these concerns, postpartum women ended up being satisfied with all items except the short duration of their hospital stay.

Geographic Variation in Overscreening for Colorectal, Cervical, and Breast Cancer Among Older Adults.

Importance: National guidelines balance risks and benefits of population-level cancer screening among adults with average risk. Older adults are not recommended to receive routine screening, but many continue to be screened (ie, are overscreened). Objective: To assess the prevalence of overscreening for colorectal, cervical, and breast cancers among older adults as well as differences in overscreening by metropolitan status. Design, Setting, and Participants: The cross-sectional study examined responses to a telephone survey of 176 348 community-dwelling adults. Participants were included if they met age and sex criteria, and they were excluded from each cancer-specific subsample if they had a history of that cancer. Data came from the 2018 Behavioral Risk Factor Surveillance System, administered by the US Centers for Disease Control and Prevention. Exposures: Metropolitan status, according to whether participants lived in a metropolitan statistical area. Main Outcomes and Measures: Overscreening was assessed using US Preventive Services Task Force definitions, ie, whether participants self-reported having a screening after the recommended upper age limit for colorectal (75 years), cervical (65 years), or breast (74 years) cancer. Results: Of 176 348 participants (155 411 [88.1%] women; mean [SE] age, 75.0 [0.04] years; 150 871 [85.6%] non-Hispanic white; 60 456 [34.3%] with nonmetropolitan residence) the cancer-specific subsamples contained 20 937 [11.9%] men and 34 244 [19.4%] women for colorectal cancer, 82 811 [47.0%] women for cervical cancer, and 38 356 [21.8%] women for breast cancer. Overall, 9461 men (59.3%; 95% CI, 57.6%-61.1%) were overscreened for colorectal cancer; 14 463 women (56.2%; 95% CI, 54.7%-57.6%), for colorectal cancer; 31 988 women (45.8%; 95% CI, 44.9%-46.7%), for cervical cancer; and 26 198 women (74.1%; 95% CI, 73.0%-75.3%), for breast cancer. Overscreening was more common in metropolitan than nonmetropolitan areas for colorectal cancer among women (adjusted odds ratio [aOR], 1.23; 95% CI, 1.08-1.39), cervical cancer (aOR, 1.20; 95% CI, 1.11-1.29), and breast cancer (aOR, 1.36; 95% CI, 1.17-1.57). Overscreening for cervical and breast cancers was also associated with having a usual source of care compared with not (eg, cervical cancer: aOR, 1.87; 95% CI, 1.56-2.25; breast cancer: aOR, 2.08; 95% CI, 1.58-2.76), good, very good, or excellent self-reported health compared with fair or poor self-reported health (eg, cervical cancer: aOR, 1.21; 95% CI, 1.11-1.32; breast cancer: aOR, 1.47; 95% CI, 1.28-1.69), an educational attainment greater than a high school diploma compared with a high school diploma or less (eg, cervical cancer: aOR, 1.14; 95% CI, 1.06-1.23; breast cancer: aOR, 1.30; 95% CI, 1.16-1.46), and being married or living as married compared with other marital status (eg, cervical cancer: OR, 1.36; 95% CI, 1.26-1.46; breast cancer: OR, 1.54; 95% CI, 1.34-1.77). Conclusions and Relevance: In this study, overscreening for cancer among older adults was high, particularly for women living in metropolitan areas. Overscreening could be associated with health care access and patient-clinician relationships. Additional research on why overscreening persists and how to reduce overscreening is needed to minimize risks associated with cancer screening among older adults.

A Framework for Effective Application of Machine Learning to Microbiome-Based Classification Problems.

Machine learning (ML) modeling of the human microbiome has the potential to identify microbial biomarkers and aid in the diagnosis of many diseases such as inflammatory bowel disease, diabetes, and colorectal cancer. Progress has been made toward developing ML models that predict health outcomes using bacterial abundances, but inconsistent adoption of training and evaluation methods call the validity of these models into question. Furthermore, there appears to be a preference by many researchers to favor increased model complexity over interpretability. To overcome these challenges, we trained seven models that used fecal 16S rRNA sequence data to predict the presence of colonic screen relevant neoplasias (SRNs) (n = 490 patients, 261 controls and 229 cases). We developed a reusable open-source pipeline to train, validate, and interpret ML models. To show the effect of model selection, we assessed the predictive performance, interpretability, and training time of L2-regularized logistic regression, L1- and L2-regularized support vector machines (SVM) with linear and radial basis function kernels, a decision tree, random forest, and gradient boosted trees (XGBoost). The random forest model performed best at detecting SRNs with an area under the receiver operating characteristic curve (AUROC) of 0.695 (interquartile range [IQR], 0.651 to 0.739) but was slow to train (83.2 h) and not inherently interpretable. Despite its simplicity, L2-regularized logistic regression followed random forest in predictive performance with an AUROC of 0.680 (IQR, 0.625 to 0.735), trained faster (12 min), and was inherently interpretable. Our analysis highlights the importance of choosing an ML approach based on the goal of the study, as the choice will inform expectations of performance and interpretability.IMPORTANCE Diagnosing diseases using machine learning (ML) is rapidly being adopted in microbiome studies. However, the estimated performance associated with these models is likely overoptimistic. Moreover, there is a trend toward using black box models without a discussion of the difficulty of interpreting such models when trying to identify microbial biomarkers of disease. This work represents a step toward developing more-reproducible ML practices in applying ML to microbiome research. We implement a rigorous pipeline and emphasize the importance of selecting ML models that reflect the goal of the study. These concepts are not particular to the study of human health but can also be applied to environmental microbiology studies.

Feasibility of Nonanonymous Burnout Surveys in a Large Academic Department.

BACKGROUND AND OBJECTIVES: Burnout is prevalent among clinicians and entails negative personal, professional, and organizational consequences. Assessments of burnout are typically anonymous to facilitate psychological safety. This limits the capacity of leadership to help struggling providers and reduces the level of demographic detail. Nonanonymous, confidential assessments may facilitate outreach to individuals or targeted interventions for at-risk populations. METHODS: We administered the Maslach Burnout Inventory to physician faculty and advanced practice providers in an academic department of family medicine. We identified a wellness officer within the department who served as an honest broker to keep nonanonymous survey responses confidential. Respondents had the option of taking the survey anonymously or confidentially. Anonymous respondents were allowed to withhold demographic information to ensure anonymity. RESULTS: Sixty-seven of 109 providers responded (61% response rate), with 46 (69%) doing so confidentially. Burnout rates were similar between groups: 48% among confidential respondents, and 43% among anonymous respondents (P=.71). Subscales of the MBI also showed no significant differences. Because a large proportion of anonymous respondents withheld demographic data, no demographic trends could be identified among them. Younger confidential respondents were more likely to exhibit depersonalization (P=.01). CONCLUSIONS: Most participants chose to respond confidentially. There was no significant difference in the level of burnout between confidential and anonymous respondents. Our findings refute the conventional wisdom that clinicians require anonymity to respond to burnout surveys. This finding has the potential to open a new line of inquiry regarding burnout, its drivers and potential solutions.

A Multi-level Model to Understand Cervical Cancer Disparities in Appalachia.

The Appalachian region experiences higher incidence and mortality due to cervical cancer compared with other regions of the United States. The goal of the Ohio State University Center for Population Health and Health Disparities (CPHHD), called the Community Awareness Resources and Education (CARE) project, was to understand reasons for this disparity. The first wave (2003-2008) of funding included three projects focusing on the known risk factors for cervical cancer, lack of screening, smoking, and infection with human papillomavirus (HPV). On the basis of the results of these projects, the second wave (2011-2017) included four projects, designed to address a multi-level model of factors contributing to cervical disparities in Appalachia. The results of these projects were then used to refine a multi-level model that explains cervical cancer disparities in Appalachia. Future funded projects will take these multi-level explanations for cervical disparities and focus on implementation science strategies to reduce the burden of cervical cancer morbidity and mortality in Appalachia.See all articles in this Special Collection Honoring Paul F. Engstrom, MD, Champion of Cancer Prevention.

The vaginal microbiota, high-risk human papillomavirus infection, and cervical cytology: results from a population-based study.

BACKGROUND: The relationship between the vaginal microbiota, high-risk human papillomavirus infection, and abnormal cervical cytology has not been well characterized. Our objective was to characterize the vaginal microbiota in a stratified random sample of women from a population-based study in Appalachia. METHODS: We analyzed a random sample of 308 women in the Community Access, Resources and Education: Project 3 study across 16 clinics in Ohio and West Virginia. Using Illumina MiSeq sequencing of 16S rRNA gene amplicons, we characterized the vaginal microbiota among (I) 109 women randomly chosen with abnormal cervical cytology (i.e., the majority were atypical squamous cells of undetermined significance (n=55) and low-grade squamous intraepithelial lesions (n=45) while n=6 were high-grade squamous intraepithelial lesions and n=3 were atypical glandular cells); (II) 110 high-risk human papillomavirus infection only without cytologic abnormality; and (III) 89 women from a stratified random sample without cytologic abnormalities (negative for intraepithelial lesion or malignancy or any human papillomavirus infection). Among the women with abnormal cervical cytology (n=109), 80 had human papillomavirus infection, the majority of which were positive for a high-risk type (n=61). RESULTS: Nearly all of the women were non-Hispanic White (94.5%), and the mean age was 26 (IQR=21-39) years. Women with abnormal cervical cytology or who were HPV+ were more likely to have a diverse vaginal microbiota characterized by higher Gardnerella vaginalis relative abundance, compared to women without cytologic abnormalities whose communities were more likely to be Lactobacillus spp. dominant (P<0.04). Women without cytologic abnormalities had a higher prevalence of L. iners dominated communities than women with abnormal cervical cytology and HR HPV+ respectively (P<0.04), and L. gasseri relative abundance was differentially greater among these women compared to women with abnormal cervical cytology or who were high-risk HPV+ (Linear discriminant analysis effect size =4.17; P=0.0009). After adjustment for age, white race, current smoking, and ≥2 male partners in the last year, however, we did not detect differences in the vaginal microbiota community states across the three outcome groups. CONCLUSIONS: Compared to women without cytologic abnormalities, the vaginal microbiota of women with abnormal cervical cytology or who were high-risk HPV+ were characterized by a diverse community with increased relative abundance of G. vaginalis and reduced relative abundance of L. gasseri. However, these differences were attenuated after adjustment for other factors. Further study and validation of these differences for prognostic use is warranted.

Inherited alterations of TGF beta signaling components in Appalachian cervical cancers.

PURPOSE: This study examined targeted genomic variants of transforming growth factor beta (TGFB) signaling in Appalachian women. Appalachian women with cervical cancer were compared to healthy Appalachian counterparts to determine whether these polymorphic alleles were over-represented within this high-risk cancer population, and whether lifestyle or environmental factors modified the aggregate genetic risk in these Appalachian women. METHODS: Appalachian women's survey data and blood samples from the Community Awareness, Resources, and Education (CARE) CARE I and CARE II studies (n = 163 invasive cervical cancer cases, 842 controls) were used to assess gene-environment interactions and cancer risk. Polymorphic allele frequencies and socio-behavioral demographic measurements were compared using t tests and χ2 tests. Multivariable logistic regression was used to evaluate interaction effects between genomic variance and demographic, behavioral, and environmental characteristics. RESULTS: Several alleles demonstrated significant interaction with smoking (TP53 rs1042522, TGFB1 rs1800469), alcohol consumption (NQO1 rs1800566), and sexual intercourse before the age of 18 (TGFBR1 rs11466445, TGFBR1 rs7034462, TGFBR1 rs11568785). Interestingly, we noted a significant interaction between "Appalachian self-identity" variables and NQO1 rs1800566. Multivariable logistic regression of cancer status in an over-dominant TGFB1 rs1800469/TGFBR1 rs11568785 model demonstrated a 3.03-fold reduction in cervical cancer odds. Similar decreased odds (2.78-fold) were observed in an over-dominant TGFB1 rs1800469/TGFBR1 rs7034462 model in subjects who had no sexual intercourse before age 18. CONCLUSIONS: This study reports novel associations between common low-penetrance alleles in the TGFB signaling cascade and modified risk of cervical cancer in Appalachian women. Furthermore, our unexpected findings associating Appalachian identity and NQO1 rs1800566 suggests that the complex environmental exposures that contribute to Appalachian self-identity in Appalachian cervical cancer patients represent an emerging avenue of scientific exploration.