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Perspective on this Article from Chromoendoscopy Detects More Adenomas than Colonoscopy Using Intensive Inspection without Dye Spraying

LeFSe analysis for adenoma vs. carcinoma clinical groups. LDA values are represented for OTUs enriched in adenoma and carcinoma clinical groups.

Diet, nutritional status, and certain dietary supplements are postulated to influence the development and progression of prostate cancer. Angiogenesis and inflammation are central to tumor growth and progression, but the effect of diet on these processes remains uncertain. We explored changes in 50 plasma cytokines and angiogenic factors (CAF) in 145 men with prostate cancer enrolled in a preoperative, randomized controlled phase II trial with four arms: control (usual diet), low-fat (LF) diet, flaxseed-supplemented (FS) diet, and FS+LS diet. The mean duration of dietary intervention was 30 to 31 days. Among the individual arms, the largest number of significant changes (baseline vs. preoperative follow-up) was observed in the LF arm, with 19 CAFs decreasing and one increasing (P < 0.05). Compared with the control arm, 6 CAFs—including proangiogenic factors (stromal-cell derived-1α) and myeloid factors (granulocyte-colony-stimulating factor, macrophage colony-stimulating factor)—all decreased in the LF arm compared with controls; three and four CAFs changed in the FS and FS+LF arms, respectively. Weight loss occurred in the LF arms and significantly correlated with VEGF decreases (P < 0.001). The CAFs that changed in the LF arm are all known to be regulated by NF-κB, and a pathway analysis identified NF-κB as the most likely regulatory network associated with these changes in the LF arm but not in the FS-containing arms. These results suggest that a LF diet without flaxseed may reduce levels of specific inflammatory CAFs and suggests that the NF-κB pathway may be a mediator of these changes. Cancer Prev Res; 4(10); 1590–8. ©2011 AACR.

The microbiome has been implicated in the development of colorectal cancer and inflammatory bowel diseases. The specific traits of these diseases vary along the axis of the digestive tract. Further, variation in the structure of the gut microbiota has been associated with both diseases. We profiled the microbiota of the healthy proximal and distal mucosa and lumen to better understand how bacterial populations vary along the colon. We used a two-colonoscope approach to sample proximal and distal mucosal and luminal contents from the colons of 20 healthy subjects that had not undergone any bowel preparation procedure. The biopsies and home-collected stool were subjected to 16S rRNA gene sequencing, and random forest classification models were built using taxa abundance and location to identify microbiota specific to each site. The right mucosa and lumen had the most similar community structures of the five sites we considered from each subject. The distal mucosa had higher relative abundance of Finegoldia, Murdochiella, Peptoniphilus, Porphyromonas, and Anaerococcus. The proximal mucosa had more of the genera Enterobacteriaceae, Bacteroides, and Pseudomonas. The classification model performed well when classifying mucosal samples into proximal or distal sides (AUC = 0.808). Separating proximal and distal luminal samples proved more challenging (AUC = 0.599), and specific microbiota that differentiated the two were hard to identify. By sampling the unprepped colon, we identified distinct bacterial populations native to the proximal and distal sides. Further investigation of these bacteria may elucidate if and how these groups contribute to different disease processes on their respective sides of the colon. Cancer Prev Res; 11(7); 393–402. ©2018 AACR.

Recent studies have suggested that the gut microbiome may be an important factor in the development of colorectal cancer. Abnormalities in the gut microbiome have been reported in patients with colorectal cancer; however, this microbial community has not been explored as a potential screen for early-stage disease. We characterized the gut microbiome in patients from three clinical groups representing the stages of colorectal cancer development: healthy, adenoma, and carcinoma. Analysis of the gut microbiome from stool samples revealed both an enrichment and depletion of several bacterial populations associated with adenomas and carcinomas. Combined with known clinical risk factors of colorectal cancer (e.g., BMI, age, race), data from the gut microbiome significantly improved the ability to differentiate between healthy, adenoma, and carcinoma clinical groups relative to risk factors alone. Using Bayesian methods, we determined that using gut microbiome data as a screening tool improved the pretest to posttest probability of adenoma more than 50-fold. For example, the pretest probability in a 65-year-old was 0.17% and, after using the microbiome data, this increased to 10.67% (1 in 9 chance of having an adenoma). Taken together, the results of our study demonstrate the feasibility of using the composition of the gut microbiome to detect the presence of precancerous and cancerous lesions. Furthermore, these results support the need for more cross-sectional studies with diverse populations and linkage to other stool markers, dietary data, and personal health information. Cancer Prev Res; 7(11); 1112–21. ©2014 AACR.

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PDF file - 95K, Flow Diagram of a Trial of Ginger Supplementation Over Four Weeks on Markers of Apoptosis, Proliferation and Differentiation in the Normal-Appearing Colorectal Mucosa of Individuals at Increased Risk of CRC

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Location and relative abundance of cancer-associated OTUs.

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Perspective on This Article from Microsatellite Instability and DNA Mismatch Repair Protein Deficiency in Lynch Syndrome Colorectal Polyps

LeFSe analysis for healthy vs. colonic lesion clinical groups. Adenoma and carcinoma clinical groups were combined into one clinical group (colonic lesion clinical group). LDA values are represented for OTUs enriched in healthy and combined colonic lesions clinical groups.

LeFSe analysis for healthy vs. carcinoma clinical groups. LDA values are represented for OTUs enriched in healthy and carcinoma clinical groups.

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Background: Recommendations for high-risk human papillomavirus (HR-HPV) testing as an adjunct to cytology for cervical cancer screening differ by age group, because HR-HPV tests lack adequate specificity in women aged Methods: Women ages 18 to 69 (n = 1,658) were enrolled and completed structured interviews to elicit data on behavioral risk factors prior to their examinations. HPV genotyping was done on exfoliated cervical cell samples. We estimated relative risks (RR) for HPV types and cofactors for CIN3+, overall and stratified by age group.Results: After 2 years of follow-up, we identified 178 CIN3+, 1,305 CIN0–2, and 175 indeterminate outcomes. Nonvaccine HR-HPV types were only associated with CIN3+ among women ≥30 (RR = 2.3, 95% CI: 1.5–3.4; Ptrend for increasing parity = 0.07). However, the parity association differed by age group (≥30: RR = 1.8, Ptrend = 0.008; Ptrend =.55).Conclusion: Subgroup variation by age in the risk of CIN3+ points to the importance of the timing of exposures in relation to CIN3+ detection.Impact: Future screening strategies need to consider natural history and secular trends in cofactor prevalence in the pursuit of appropriately sensitive and specific screening tools applied to appropriate age groups. Cancer Epidemiol Biomarkers Prev; 21(1); 111–21. ©2011 AACR.

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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.

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.

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. Supplementary Information The online version contains supplementary material available at 10.1007/s13187-021-02069-0.

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.

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.

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. But Bayesian designs, capable of incorporating information external to the experiment, provide a dynamic translational strategy. The current 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 E(2), 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 the 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 ten to 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: Three 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.

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.

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.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).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 higherCompared 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

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.

Nonalcoholic fatty liver disease is the leading cause of liver disease worldwide and can progress to nonalcoholic steatohepatitis (NASH) through physical inactivity and gut dysbiosis.1 Exercise training reverses gut dysbiosis in non-NASH persons with obesity and in NASH animal models.2,3 Consequently, we conducted a proof-of-concept study investigating the effect of exercise training on gut dysbiosis in NASH patients.

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 chi-square 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/TFBR1 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 represents an emerging avenue of scientific exploration.

BACKGROUND: The intestinal microbiome is an important determinant of inflammatory balance in the colon that may affect response to dietary agents. OBJECTIVE: This is a secondary analysis of a clinical trial, the Fish Oil Study, to determine whether interindividual differences in colonic bacteria are associated with variability in the reduction of colonic prostaglandin E(2) (PGE(2)) concentrations after personalized supplementation with ω-3 (n–3) fatty acids. METHODS: Forty-seven healthy adults (17 men, 30 women, ages 26–75 y) provided biopsy samples of colonic mucosa and luminal stool brushings before and after personalized ω-3 fatty acid supplementation that was based on blood fatty acid responses. Samples were analyzed using 16S ribosomal RNA sequencing. The data analyses focused on changes in bacterial community diversity. Linear regression was used to evaluate factors that predict a reduction in colonic PGE(2). RESULTS: At baseline, increased bacterial diversity, as measured by the Shannon and Inverse Simpson indexes in both biopsy and luminal brushing samples, was positively correlated with dietary fiber intakes and negatively correlated with fat intakes. Dietary supplementation with ω-3 fatty acids increased the Yue and Clayton community dis-similarity index between the microbiome in luminal brushings and colon biopsy samples post-supplementation (P = 0.015). In addition, there was a small group of individuals with relatively high Prevotella abundance who were resistant to the anti-inflammatory effects of ω-3 fatty acid supplementation. In linear regression analyses, increases in diversity of the bacteria in the luminal brushing samples, but not in the biopsy samples, were significant predictors of lower colonic PGE(2) concentrations post-supplementation in models that included baseline PGE(2), baseline body mass index, and changes in colonic eicosapentaenoic acid–to–arachidonic acid ratios. The changes in bacterial diversity contributed to 6–8% of the interindividual variance in change in colonic PGE(2) (P = 0.001). CONCLUSIONS: Dietary supplementation with ω-3 fatty acids had little effect on intestinal bacteria in healthy humans; however, an increase in diversity in the luminal brushings significantly predicted reductions in colonic PGE(2). This trial was registered at www.clinicaltrials.gov as NCT 01860352.

In the United States (U.S.), only five states or territories require human papillomavirus (HPV) vaccination for school attendance, even though almost all U.S. jurisdictions have debated adopting this type of policy. In this U.S. based study, we sought to estimate the level of support for HPV vaccine school-entry requirements with varying exemption policies and documentation procedures to obtain exemptions. Between July and August 2019, we conducted a web-based survey with a national sample of 1,109 U.S. parents of 11- to 17-year-olds. The survey assessed support for four school-entry vaccine requirement policies: without exemption or with exemption for medical, religious or philosophical reasons. Analyses used multivariable logistic regression to assess correlates of support for each policy. Overall, 38% of parents agreed with laws requiring HPV vaccination for school attendance without exemptions. When including exemption provisions, agreement increased to 45% for philosophical reasons, 50% for religious reasons, and 59% for medical reasons. Parents more often agreed on requirements without any exemptions if they were female (OR = 1.37, 95% CI:1.01-1.87), their child had initiated HPV vaccination (OR = 2.05, 95% CI:1.50-2.87), reported high levels of vaccine confidence (OR = 2.41, 95% CI:1.77-3.27), or reported having values similar to those of the people in their community (OR = 1.85, 95% CI:1.39-2.47). Parents more often agreed with requirements that included religious or philosophical exemptions if they reported having values similar to their community or high levels of psychological reactance (all p .05). Many parents also supported requiring a written notice signed by a health care provider (40%) or religious leader (49%) to obtain a medical or religious exemption, respectively. In conclusion, exemption policies greatly increase parent support of school-entry requirements for HPV vaccination but may decrease their impact in practice. A large number of U.S. parents support strict documentation to obtain exemptions, signaling a promising area of policymaking to strengthen vaccine policies for school attendance.

Appalachian women 18 to 26 years old have high baseline seropositivity rates for at least 1 of the 4 human papillomavirus vaccine–related types, but low vaccine-relevant type infections. Supplemental digital content is available in the text., 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.

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 E(2) (PGE(2)), 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 PGE(2). 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 PGE(2) 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 PGE(2) versus 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.

Aim: We sought to explore how early adopters use pharmacogenomic (PGx) testing for treating depression and attention-deficit/hyperactivity disorder. Patients & methods: Prescribers of the Informed PGx (Progenity, Inc., Ann Arbor, MI 48108, USA) test completed a phone survey assessing use of PGx testing for different scenarios. We conducted a qualitative thematic text analysis of transcribed audio recordings of open-ended responses (n = 62). Results: PGx testing was used when treating multiple comorbidities or resistant disease, and to ease patients’ concerns with future therapy. Use of PGx testing is influenced by insurance coverage, interpretability of results and results turnaround time. Conclusion: Prescribers used PGx tests to modify medications for complex patients with depression, attention-deficit/hyperactivity disorder and other disorders to alleviate concerns related to adverse effects and lack of effectiveness.

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.]

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.

ObjectiveThe Community Awareness Resources and Education (CARE) project: Reducing Cervical Cancer in Appalachia is part of the NIH Centers for Population Health and Health Disparities initiative. It aims to increase screening rates for cervical cancer, to assist in tobacco cessation, and to determine the role of human papillomavirus (HPV) in contributing to the increased risk of cervical cancer.MethodsEligible subjects were recruited from 14 clinics in Appalachian Ohio. CARE’s cross sectional survey (CS) (571 participants) characterized social, behavioral, and environmental factors of Pap smear screening and smoking. The intervention projects tested programs to increase Pap smear screening (280 participants) or aid in smoking cessation (300 participants). A case control study (1360 participants) assessed social, behavioral, and biologic predictors of abnormal Pap tests.ResultsThe CS participants tended to be younger, more educated, and were more likely to be employed than the general population of Appalachian women 18 and over. They were similar to the other samples in terms of race, marital status, income level and smoking status.ConclusionsCARE will provide valuable information about the multi-level barriers to obtaining regular Pap smears and quitting smoking, as well as help to identify important biological and social risk factors related to abnormal Pap smears.

Colorectal cancer (CRC) is a leading cause of cancer-related deaths in both the USA and the world. Recent research has demonstrated the involvement of the gut microbiota in CRC development and progression. Microbial biomarkers of disease have focused primarily on the bacterial component of the microbiome; however, the viral portion of the microbiome, consisting of both bacteriophages and eukaryotic viruses, together known as the virome, has been lesser studied. Here we review the recent advancements in high-throughput sequencing (HTS) technologies and bioinformatics, which have enabled scientists to better understand how viruses might influence the development of colorectal cancer. We discuss the contemporary findings revealing modulations in the virome and their correlation with CRC development and progression. While a variety of challenges still face viral HTS detection in clinical specimens, we consider herein numerous next steps for future basic and clinical research. Clinicians need to move away from a single infectious agent model for disease etiology by grasping new, more encompassing etiological paradigms, in which communities of various microbial components interact with each other and the host. The reporting and indexing of patient health information, socioeconomic data, and other relevant metadata will enable identification of predictive variables and covariates of viral presence and CRC development. Altogether, the virome has a more profound role in carcinogenesis and cancer progression than once thought, and viruses, specific for either human cells or bacteria, are clinically relevant in understanding CRC pathology, patient prognosis, and treatment development.

This clinical trial developed a personalized dosing model for reducing prostaglandin E2 (PGE2) in colonic mucosa using ω-3 fatty acid supplementation. The model utilized serum eicosapentaenoic acid (EPA, ω-3):arachidonic acid (AA, ω-6) ratios as biomarkers of colonic mucosal PGE2 concentration. Normal human volunteers were given low and high ω-3 fatty acid test doses for 2 weeks. This established a slope and intercept of the line for dose versus serum EPA:AA ratio in each individual. The slope and intercept was utilized to calculate a personalized target dose that was given for 12 weeks. This target dose was calculated on the basis of a model, initially derived from lean rodents, showing a log-linear relationship between serum EPA:AA ratios and colonic mucosal PGE2 reduction. Bayesian methods allowed addition of human data to the rodent model as the trial progressed. The dosing model aimed to achieve a serum EPA:AA ratio that is associated with a 50% reduction in colonic PGE2. Mean colonic mucosal PGE2 concentrations were 6.55 ng/mg protein (SD, 5.78) before any supplementation and 3.59 ng/mg protein (SD, 3.29) after 12 weeks of target dosing. In secondary analyses, the decreases in PGE2 were significantly attenuated in overweight and obese participants. This occurred despite a higher target dose for the obese versus normal weight participants, as generated by the pharmacodynamic predictive model. Large decreases also were observed in 12-hydroxyicosatetraenoic acids, and PGE3 increased substantially. Future biomarker-driven dosing models for cancer prevention therefore should consider energy balance as well as overall eicosanoid homeostasis in normal tissue. Cancer Prev Res; 10(12); 729–37. ©2017 AACR.