Racial disparities in colorectal cancer outcomes and access to care: a multi-cohort analysis.

Introduction: Non-Hispanic Black (NHB) Americans have a higher incidence of colorectal cancer (CRC) and worse survival than non-Hispanic white (NHW) Americans, but the relative contributions of biological versus access to care remain poorly characterized. This study used two nationwide cohorts in different healthcare contexts to study health system effects on this disparity. Methods: We used data from the Surveillance, Epidemiology, and End Results (SEER) registry as well as the United States Veterans Health Administration (VA) to identify adults diagnosed with colorectal cancer between 2010 and 2020 who identified as non-Hispanic Black (NHB) or non-Hispanic white (NHW). Stratified survival analyses were performed using a primary endpoint of overall survival, and sensitivity analyses were performed using cancer-specific survival. Results: We identified 263,893 CRC patients in the SEER registry (36,662 (14%) NHB; 226,271 (86%) NHW) and 24,375 VA patients (4,860 (20%) NHB; 19,515 (80%) NHW). In the SEER registry, NHB patients had worse OS than NHW patients: median OS of 57 months (95% confidence interval (CI) 55-58) versus 72 months (95% CI 71-73) (hazard ratio (HR) 1.14, 95% CI 1.12-1.15, p = 0.001). In contrast, VA NHB median OS was 65 months (95% CI 62-69) versus NHW 69 months (95% CI 97-71) (HR 1.02, 95% CI 0.98-1.07, p = 0.375). There was significant interaction in the SEER registry between race and Medicare age eligibility (p < 0.001); NHB race had more effect in patients <65 years old (HR 1.44, 95% CI 1.39-1.49, p < 0.001) than in those ≥65 (HR 1.13, 95% CI 1.11-1.15, p < 0.001). In the VA, age stratification was not significant (p = 0.21). Discussion: Racial disparities in CRC survival in the general US population are significantly attenuated in Medicare-aged patients. This pattern is not present in the VA, suggesting that access to care may be an important component of racial disparities in this disease.

Cancer Screening in Low- and Middle-Income Countries.

The worldwide cancer burden is growing, and populations residing in low- and middle-income countries (LMICs) are experiencing a disproportionate extent of this growth. Breast, colorectal, and cervical cancers are among the top 10 most frequently diagnosed malignancies, and they also account for a substantial degree of cancer mortality internationally. Effective screening strategies are available for all three of these cancers. Individuals from LMICs face substantial cost and access barriers to early detection programs, and late stage at diagnosis continues to be a major cause for cancer mortality in these communities. This chapter will review the epidemiology of breast, colorectal, and cervical cancers, and will explore prospects for improving global control through novel approaches to screening in cost-constrained environments.

Distribution of COVID-19 Home Testing Through Community Health Centers: Results of the COVID CoNOce MÁS Study.

OBJECTIVE: To assess acceptability and feasibility of rapid at-home COVID-19 testing and reporting of test results among individuals seeking care at community health centers (CHCs) and their household members. METHODS: Participants were recruited from 2 Community Health Centers during a clinic visit or a community event. Over-the-counter COVID-19 tests were distributed to participants for self-testing and to offer testing to household members. Separate surveys were administered to collect baseline information on the study participant and to collect test results on the study participant and household members. We calculated the proportion of individuals who agreed to complete COVID home testing, those who reported test results, and the test positivity. For household members, we calculated the proportion who completed and reported results and the positivity rate. We assessed reasons for undergoing COVID-19 testing and the action taken by participants who reported positive tests. RESULTS: A total of 2189 individuals were approached by CHC staff for participation and 1013 (46.3%) agreed to participate. Among the 959 participants with complete sociodemographic data, 88% were Hispanic and 82.6% were female. The proportion providing test results was 36.2% and the test positivity was 4.2%. Among the 1927 test reports, 35.3% for the index participant and 64.4% were for household members. The largest proportion of test results were for index participants (35.3%) and the second largest was for the participant's children (32.1%), followed by parents (16.9%), and spouse/partner (13.2%). The 2 most common reasons for testing were symptoms (29%) and attending family gatherings (26%). Among test-positive individuals (n = 80), most (83.3%) noted that they isolated but only 16.3% called their provider and 1.3% visited a clinic. CONCLUSION: Our results show interest in at-home COVID-19 testing of multiple household members, as we headed into the endemic phase of the pandemic. However, reporting of test results was modest and among test-positive individuals, reporting results to a provider was very low. These results underscore the challenges with reporting and following guidelines among people undergoing home testing for COVID-19, which may have implications for future pandemics.

A pragmatic randomized trial of mailed fecal immunochemical testing to increase colorectal cancer screening among low-income and minoritized populations.

BACKGROUND: Colorectal cancer (CRC) screening is underused, particularly among low-income and minoritized populations, for whom the coronavirus disease 2019 (COVID-19) pandemic has challenged progress in achieving equity. METHODS: A hub-and-spoke model was used. The hub was a nonacademic organization and the spokes were three community health center (CHC) systems overseeing numerous clinic sites. Via a cluster-randomized trial design, nine clinic sites were randomized to intervention and 16 clinic sites were randomized to usual care. Patient-level interventions included invitation letters, mailed fecal immunochemical tests (FITs), and call/text-based reminders. Year 1 intervention impact, which took place during the COVID-19 pandemic, was assessed as the proportion completing screening among individuals not up to date at baseline, which compared intervention and nonintervention clinics accounting for intraclinic cluster variation; confidence intervals (CIs) around differences not including 0 were interpreted as statistically significant. RESULTS: Among 26,736 patients who met eligibility criteria, approximately 58% were female, 55% were Hispanic individuals, and 44% were Spanish speaking. The proportion completing screening was 11.5 percentage points (ppts) (95% CI, 6.1-16.9 ppts) higher in intervention versus usual care clinics. Variation in differences between intervention and usual care clinics was observed by sex (12.6 ppts [95% CI, 7.2-18.0 ppts] for females; 8.8 ppts [95% CI, 4.7-13.9 ppts] for males) and by racial and ethnic group (13.8 ppts [95% CI, 7.0-20.6 ppts] for Hispanic individuals; 13.0 ppts [95% CI, 3.6-22.4 ppts] for Asian individuals; 11.3 ppts [95% CI, 5.8-16.8 ppts] for non-Hispanic White individuals; 6.1 ppts [95% CI, 0.8-10.4 ppts] for Black individuals). CONCLUSIONS: A regional mailed FIT intervention was effective for increasing CRC screening rates across CHC systems serving diverse, low-income populations.

Mental health and social connection among older lesbian and bisexual women.

OBJECTIVE: To assess differences in psychosocial and mental health outcomes between older lesbian and bisexual women compared to heterosexual women. DESIGN: Cross sectional study. SETTING: The study was carried out in the California Teachers Study, a prospective cohort study. PARTICIPANTS: Self-identified heterosexual (n = 35,846), lesbian (n = 710), and bisexual (n = 253) women 50 years of age and older were enrolled. MEASUREMENTS: Validated questionnaires were used to measure social connection, overall happiness, and depression. Logistic regression modeling was used to estimate odds ratios (OR) and 95% confidence intervals (CI) comparing lesbian and bisexual women separately to heterosexual women in relation to psychosocial and mental health outcomes. RESULTS: After controlling for age and marital status, older bisexual women were significantly more likely to report lack of companionship (OR = 2.00; 95% CI, 1.30-3.12) and feeling left out (OR = 2.33; 95% CI, 1.36-3.97) compared to older heterosexual women. The odds of reporting feeling isolated from others was significantly higher in lesbian (OR = 1.56; 95% CI, 1.06-2.30) and bisexual women (OR = 2.30; 95% CI, 1.37-3.87) than in heterosexual women. The OR (95% CI) for reporting not being very happy overall was 1.96 (CI, 1.09-3.52) in bisexual women and 1.40 (0.92-2.14) in lesbian women compared to heterosexual women. The likelihood of reporting diagnosed depression was significantly higher in lesbian women (OR = 1.65; 95% CI, 1.38-1.97) and bisexual women (OR = 2.21; 95% CI, 1.67-2.93) compared to heterosexual women. CONCLUSION: Inclusion of lesbian and bisexual women in aging research is essential to understand their unique mental and other health needs, including those specific to bisexual women.

Social Determinants of Health and Informed Consent Comprehension for Pediatric Cancer Clinical Trials.

Importance: Ensuring valid informed consent (IC) prior to enrollment in clinical trials is a fundamental ethical right. Objective: To assess whether social determinants of health (SDOH) and related sociocontextual factors are associated with parental IC comprehension in therapeutic childhood cancer clinical trials. Design, Setting, and Participants: This cross-sectional study prospectively enrolled 223 parents of children with newly diagnosed cancer at Rady Children's Hospital San Diego, a large quaternary academic center in California, from October 1, 2014, to March 31, 2021. Linear mixed effects models were used to assess whether IC comprehension overall and by domain (purpose, procedures, and randomization; risks and benefits; alternatives; and voluntariness) were associated with SDOH and sociocontextual factors. Data were analyzed from January 1, 2022, to July 31, 2023. Exposures: Informed consent for a therapeutic childhood cancer clinical trial. Main Outcomes and Measures: The primary outcome of interest was IC comprehension and its associations with SDOH (marital status, language, educational attainment, employment, insurance type, socioeconomic status, and health literacy) and sociocontextual factors (ethnicity, satisfaction with informed consent, and cancer type). Results: Of 223 parents, 172 (77.1%) were aged 18 to 44 years, 111 (49.8%) were Hispanic, 152 (68.2%) were women, and 163 (73.1%) were married. In terms of race, 2 (0.9%) were American Indian or Alaska Native, 22 (9.9%) were Asian or Pacific Islander, 8 (3.6%) were Black, 149 (66.8%) were White, and 42 (18.8%) were more than 1 race. In multivariable linear mixed-effects analyses, limited vs adequate health literacy was associated with lower comprehension of informed consent overall (mean [SD], 68.28 [11.81] vs 79.24 [11.77]; ß estimate, -9.02 [95% CI, -12.0 to -6.07]; P < .001) and with lower comprehension of the purpose, procedures, and randomization (mean [SD], 65.00 [12.64] vs 76.14 [11.53]; ß estimate, -7.87 [95% CI, -10.9 to -4.85]; P < .001); risks and benefits (mean [SD], 62.84 [20.24] vs 73.14 [20.86]; ß estimate, -10.1 [95% CI, -15.6 to -4.59]; P < .001); alternatives (mean [SD], 54.27 [43.18] vs 82.98 [34.24]; ß estimate, -14.3 [95% CI, -26.1 to -2.62]; P .02); and voluntariness (mean [SD], 76.52 [24.33] vs 95.39 [13.89]; ß estimate, -9.14 [95% CI, -14.9 to -3.44]; P = .002) domains. Use of Spanish vs English language for medical communication was associated with lower comprehension overall (mean [SD], 66.45 [12.32] vs 77.25 [12.18]; ß estimate, -5.30 [95% CI, -9.27 to -1.34]; P = .01) and with lower comprehension of the purpose, procedures, and randomization (mean [SD], 63.33 [11.98] vs 74.07 [12.52]; ß estimate, -4.33 [95% CI, -8.43 to -0.23]; P = .04) and voluntariness (mean [SD], 70.83 [24.02] vs 92.54 [17.27]; ß estimate, -9.69 [95% CI, -16.8 to -2.56]; P = .009) domains. Conclusions and Relevance: In this cross-sectional study including parents of children with newly diagnosed cancer who provided IC for their child's participation in a therapeutic clinical trial, limited health literacy and use of Spanish language for medical communication were associated with lower comprehension of IC. These findings suggest that, in this setting, parents with limited health literacy or those who use Spanish language for medical communication may not fully comprehend IC and therefore may not make truly informed decisions. These findings support the investigation of interventions, across pediatric disciplines, tailored to the participant's language and health literacy level to improve IC comprehension, particularly in racial and ethnic minority populations.

Time to Endoscopy or Colonoscopy Among Adults Younger Than 50 Years With Iron-Deficiency Anemia and/or Hematochezia in the VHA.

Importance: To date, the diagnostic test completion rate and the time to diagnostic endoscopy or colonoscopy among adults with iron-deficiency anemia (IDA) and/or hematochezia have not been well characterized. Objective: To evaluate the diagnostic test completion rate and the time to diagnostic testing among veterans younger than 50 years with IDA and/or hematochezia. Design, Setting, and Participants: This cohort study was conducted within the Veterans Health Administration between October 1, 1999, and December 31, 2019, among US veterans aged 18 to 49 years from 2 separate cohorts: those with a diagnosis of IDA (n = 59 169) and those with a diagnosis of hematochezia (n = 189 185). Statistical analysis was conducted from August 2021 to August 2023. Exposures: Diagnostic testing factors included age, sex, race and ethnicity, Veterans Health Administration geographic region, and hemoglobin test value (IDA cohort only). Main Outcomes and Measures: Primary outcomes of diagnostic testing were (1) bidirectional endoscopy after diagnosis of IDA and (2) colonoscopy or sigmoidoscopy after diagnosis of hematochezia. The association between diagnostic testing factors and diagnostic test completion was examined using Poisson models. Results: There were 59 169 veterans with a diagnosis of IDA (mean [SD] age, 40.7 [7.1] years; 30 502 men [51.6%]), 189 185 veterans with a diagnosis of hematochezia (mean [SD] age, 39.4 [7.6] years; 163 690 men [86.5%]), and 2287 veterans with IDA and hematochezia (mean [SD] age, 41.6 [6.9] years; 1856 men [81.2%]). The cumulative 2-year diagnostic workup completion rate was 22% (95% CI, 22%-22%) among veterans with IDA and 40% (95% CI, 40%-40%) among veterans with hematochezia. Veterans with IDA were mostly aged 40 to 49 years (37 719 [63.7%]) and disproportionately Black (24 480 [41.4%]). Women with IDA (rate ratio [RR], 0.42; 95% CI, 0.40-0.43) had a lower likelihood of diagnostic test completion compared with men with IDA. Black (RR, 0.65; 95% CI, 0.62-0.68) and Hispanic (RR, 0.88; 95% CI, 0.82-0.94) veterans with IDA were less likely to receive diagnostic testing compared with White veterans with IDA. Veterans with hematochezia were mostly White (105 341 [55.7%]). Among veterans with hematochezia, those aged 30 to 49 years were more likely to receive diagnostic testing than adults younger than 30 years of age (age 30-39 years: RR, 1.15; 95% CI, 1.12-1.18; age 40-49 years: RR, 1.36; 95% CI, 1.33-1.40). Hispanic veterans with hematochezia were less likely to receive diagnostic testing compared with White veterans with hematochezia (RR, 0.96; 95% CI, 0.93-0.98). Conclusions and Relevance: In the cohorts of veterans younger than 50 years with IDA and/or hematochezia, the diagnostic test completion rate was low. Follow-up was less likely among female, Black, and Hispanic veterans with IDA and Hispanic veterans with hematochezia. Optimizing timely follow-up across social and demographic groups may contribute to improving colorectal cancer outcomes and mitigate disparities.

Hub-and-Spoke centralized intervention to optimize colorectal cancer screening and follow-up: A pragmatic, cluster-randomized controlled trial protocol.

BACKGROUND: Guidelines recommend screening for colorectal cancer (CRC), but participation and abnormal test follow up rates are suboptimal, with disparities by demography. Evidence-based interventions exist to promote screening, but community adoption and implementation are limited. METHODS: The San Diego Accelerating Colorectal Cancer Screening and Follow-up through Implementation Science (ACCSIS) program is an academic-community partnership testing regional implementation of a Hub-and-Spoke model for increasing CRC screening and follow-up. The "hub" is a non-academic, non-profit organization that includes 17 community health center (CHC) systems, serving over 190 rural and urban clinic sites. The "spokes" are 3 CHC systems that oversee 11-28 clinics each, totaling over 60 clinics. Using a cluster-randomized trial design, 9 clinics were randomized to intervention and 16 to usual care. Within intervention clinics, approximately 5000 eligible patients not up-to-date with CRC screening per year were identified for intervention. Interventions include an invitation primer, a mailed fecal immunochemical test with completion instructions, and phone and text-based reminders (hub) and patient navigation protocol to promote colonoscopy completion after abnormal FIT (spoke). Outcomes include: 1) proportion of patients up-to-date with screening after three years in intervention versus non-intervention clinics; 2) proportion of patients with abnormal FIT completing colonoscopy within six months of the abnormal result. Implementation science measures are collected to assess acceptability, intervention and usual care adaptations, and sustainability of the intervention strategies. CONCLUSION: This large-scale, regional cluster randomized trial among CHCs serving diverse populations is anticipated to accelerate progress in CRC prevention in underserved populations. TRIAL REGISTRATION: NCT04941300.

Paternal developmental thyrotoxicosis disrupts neonatal leptin leading to increased adiposity and altered physiology of the melanocortin system.

Background: The genetic code does not fully explain individual variability and inheritance of susceptibility to endocrine conditions, suggesting the contribution of epigenetic factors acting across generations. Methods: We used a mouse model of developmental thyrotoxicosis (Dio3-/- mouse) to analyze endocrine outcomes in the adult offspring of Dio3-/- males using standard methods for body composition, and baseline and fasting hormonal and gene expression determinations in serum and tissues of relevance to the control of energy balance. Results: Compared to controls, adult females with an exposed father (EF females) exhibited higher body weight and fat mass, but not lean mass, a phenotype that was much milder in EF males. After fasting, both EF females and males exhibited a more pronounced decrease in body weight than controls. EF females also showed markedly elevated serum leptin, increased white adipose tissue mRNA expression of leptin and mesoderm-specific transcript but decreased expression of type 2 deiodinase. EF females exhibited decreased serum ghrelin, which showed more pronounced post-fasting changes in EF females than in control females. EF female hypothalami also revealed significant decreases in the expression of pro-opiomelanocortin, agouti-related peptide, neuropeptide Y and melanocortin receptor 4. These markers also showed larger changes in response to fasting in EF females than in control females. Adult EF females showed no abnormalities in serum thyroid hormones, but pituitary expression of thyrotropin-releasing hormone receptor 1 and thyroid gland expression of thyroid-stimulating hormone receptor, thyroid peroxidase and iodotyrosine deiodinase were increased at baseline and showed differential regulation after fasting, with no increase in Trhr1 expression and more pronounced reductions in Tshr, Tpo and Iyd. In EF males, these abnormalities were generally milder. In addition, postnatal day 14 (P14) serum leptin was markedly reduced in EF pups. Discussion: A paternal excess of thyroid hormone during development modifies the endocrine programming and energy balance in the offspring in a sexually dimorphic manner, with baseline and dynamic range alterations in the leptin-melanocortin system and thyroid gland, and consequences for adiposity phenotypes. We conclude that thyroid hormone overexposure may have important implications for the non-genetic, inherited etiology of endocrine and metabolic pathologies.

Partnering With Patients and Caregivers in Cancer Care: Lessons From Experiences With Transgender, Hispanic, and Pediatric Populations.

A cancer diagnosis thrusts patients and caregivers into a foreign world of health care with systems, protocols, and norms that can leave little room for individual needs and circumstances. Quality and efficacious oncology care requires clinicians to partner with patients and caregivers to understand and incorporate their needs, values, and priorities into information sharing, decision making, and care provision. This partnership is necessary for effective patient- and family-centered care and access to individualized and equitable information, treatment, and research participation. Partnering with patients and families also requires oncology clinicians to see that our personal values, preconceived ideas, and established systems exclude certain populations and potentially lead to poorer care for all patients. Furthermore, inequitable access to participation in research and clinical trials can contribute to an unequal burden of cancer morbidity and mortality. Leveraging the expertise of the authorship team with transgender, Hispanic, and pediatric populations, this chapter provides insights and suggestions for oncology care that are applicable across patient populations to mitigate stigma and discrimination and improve the quality of care for all patients.

HPV Vaccine Misperceptions Among Hispanics/Latinos in Southern California.

BACKGROUND: Cervical and other vaccine-preventable HPV-associated cancers disproportionately impact Hispanic/Latinos in the USA. HPV vaccine uptake may be impacted by community agreement with common HPV vaccine misperceptions. It is unknown whether Hispanics/Latinos have a greater agreement with these misperceptions relative to non-Hispanic whites. METHODS: HPV vaccine misperceptions were assessed through a 12-item Likert scale included in a population health assessment mailed to households in the southwest United States. Linear regression models assessed the association between identifying as Hispanic/Latino and summed misperception score. RESULTS: Among the 407 individuals in the analytic sample, 111 (27.3%) were Hispanic/Latino and 296 (72.7%) were non-Hispanic white. On average, Hispanics/Latinos had a 3.03-point higher HPV vaccine misperception sum score relative to non-Hispanic whites, indicating greater agreement with misperceptions (95% confidence interval: 1.16-4.88; p < 0.01). DISCUSSION: Culturally relevant interventions are needed to address HPV vaccine misperceptions among Hispanics/Latinos as part of efforts toward HPV-associated cancer health equity.

N-palmitoylethanolamide synergizes the antinociception of morphine and gabapentin in the formalin test in mice.

OBJECTIVE: The antinociceptive pharmacological interaction between N-palmitoylethanolamide (PEA) and morphine (MOR), as well as gabapentin (GBP), was investigated to obtain synergistic antinociception at doses where side effects were minimal. In addition, the possible antinociceptive mechanism of PEA + MOR or PEA + GBP combinations was explored. METHODS: Individual dose-response curves (DRCs) of PEA, MOR and GBP were evaluated in female mice in which intraplantar nociception was induced with 2% formalin. Isobolographic method was used to detect the pharmacological interaction in the combination of PEA + MOR or PEA + GBP. KEY FINDINGS: The ED50 was calculated from the DRC; the order of potency was MOR > PEA > GBP. The isobolographic analysis was obtained at a 1:1 ratio to determine the pharmacological interaction. The experimental values of flinching (PEA + MOR, Zexp = 2.72 ± 0.2 µg/paw and PEA + GBP Zexp = 2.77 ± 0.19 µg/paw) were significantly lower than those calculated theoretically (PEA + MOR Zadd = 7.78 ± 1.07 and PEA + GBP Zadd = 24.05 ± 1.91 µg/paw), resulting in synergistic antinociception. Pretreatment with GW6471 and naloxone demonstrated that peroxisome proliferator-activated receptor alpha (PPARα) and opioid receptors are involved in both interactions. CONCLUSIONS: These results suggest that MOR and GBP synergistically enhance PEA-induced antinociception through PPARα and opioid receptor mechanisms. Furthermore, the results suggest that combinations containing PEA with MOR or GBP could be of interest in aiding the treatment of inflammatory pain.

Post Treatment Mastalgia is a Common Complaint but not an Indication of Recurrence or Second Primary Breast Cancer.

BACKGROUND: Post-treatment mastalgia is a common complaint in up to 68% of patients after treatment. This symptom is worrisome to patients as many believe it is a sign of recurrence. The current study was performed to evaluate if post-treatment mastalgia is associated with a second breast cancer diagnosis. MATERIALS AND METHODS: Patients included were seen from January 1, 2000 to December 31, 2020. All patients who were treated for breast cancer and then presented with breast pain during follow up were considered to have post-treatment mastalgia. All patients who were diagnosed with a second breast cancer but did not experience post-treatment mastalagia were also evaluated. RESULTS: 1799 patients had a mean age 52.9 years. 36% of patients experienced post-treatment mastalgia. Of patients who complained of post-treatment mastalgia, 19 were diagnosed with a chest wall recurrence (CW), ipsilateral breast tumor recurrence (IBTR), or contralateral breast cancer (CBC). 17 of the 19 patients had breast pain after the second diagnosis and treatment were completed. The average duration between their second diagnosis and initial complaint of breast pain was 6.2 years. The two patients who complained of breast pain prior to their second diagnosis did not have mastalgia at the time of their second diagnosis. Local recurrence or contralateral breast cancer were more common in patients without post treatment mastalgia (10.1% vs 0.3%, p < 0.0001) during follow up. CONCLUSION: Post treatment mastalgia is not associated with recurrence. Interval or repeat imaging does not appear necessary and instead patient education and reassurance are important in its management.

Physical Activity, Sedentary Behavior, and Risk of Coronavirus Disease 2019.

INTRODUCTION: Data on the associations of prepandemic physical activity and sedentary behavior with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) severity, particularly milder illness, have been limited. METHODS: We used data from 43,913 participants within the Nurses' Health Study II and Health Professionals Follow-Up Study who responded to periodic COVID-related surveys from May 2020 through March 2021. History of physical activity from the prepandemic period was assessed as the metabolic equivalents of task (MET)-hours per week of various activities of different intensity and sedentary behavior assessed from reports of time spent sitting from questionnaires completed 2016-2017. Multivariable logistic regression models were fitted to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for risk of SARS-CoV-2 infection and COVID-19 severity, as well as predicted COVID-19 defined using a validated symptom-based algorithm. RESULTS: Higher levels of prepandemic physical activity were associated with a lower risk for SARS-CoV-2 infection. Compared to participants with <3 MET-hours per week, the multivariable-adjusted OR was 0.86 (95% CI: 0.74, 0.99; P trend =.07) for those with ≥27 MET-hours per week. Higher physical activity levels were also associated with lower risk of symptomatic SARS-CoV-2 infection (OR: 0.84; 95% CI: 0.72, 0.99; P trend = .05) and predicted COVID-19 (OR: 0.87; 95% CI: 0.78, 0.97; P trend = .01). Longer time sitting at home watching TV (OR: 0.85; 95% CI: 0.73, 0.97) or for other tasks (OR: 0.78; 95% CI: 0.66, 0.92) was associated with a lower risk of SARS-CoV-2 infection. CONCLUSIONS: Our findings support a protective association between prepandemic physical activity and lower risk and severity of COVID-19.

COVID-19 Pandemic Had Minimal Impact on Colonoscopy Completion After Colorectal Cancer Red Flag Sign or Symptoms in US Veterans.

BACKGROUND: Delays in colonoscopy work-up for red flag signs or symptoms of colorectal cancer (CRC) during the COVID-19 pandemic are not well characterized. AIMS: To examine colonoscopy uptake and time to colonoscopy after red flag diagnosis, before and during the COVID-19 pandemic. METHODS: Cohort study of adults ages 50-75 with iron deficiency anemia (IDA), hematochezia, or abnormal stool blood test receiving Veterans Health Administration (VHA) care from April 2019 to December 2020. Index date was first red flag diagnosis date, categorized into "pre" (April-December 2019) and "intra" (April-December 2020) policy implementation prioritizing diagnostic procedures, allowing for a 3-month "washout" (January-March 2020) period. Outcomes were colonoscopy completion and time to colonoscopy pre- vs. intra-COVID-19, examined using multivariable Cox models with hazard ratios (aHRs) and 95% confidence intervals (CIs). RESULTS: There were 52,539 adults with red flag signs or symptoms (pre-COVID: 25,154; washout: 7527; intra-COVID: 19,858). Proportion completing colonoscopy was similar pre- vs. intra-COVID-19 (27.0% vs. 26.5%; p = 0.24). Median time to colonoscopy among colonoscopy completers was similar for pre- vs. intra-COVID-19 (46 vs. 42 days), but longer for individuals with IDA (60 vs. 49 days). There was no association between time period and colonoscopy completion (aHR: 0.99, 95% CI 0.95-1.03). CONCLUSIONS: Colonoscopy work-up of CRC red flag signs and symptoms was not delayed within VHA during the COVID-19 pandemic, possibly due to VHA policies supporting prioritization and completion. Further work is needed to understand how COVID-19 policies on screening and surveillance impact CRC-related outcomes, and how to optimize colonoscopy completion after a red flag diagnosis.

Neighborhood Factors Associated with COVID-19 Cases in California.

BACKGROUND: There is a need to assess neighborhood-level factors driving COVID-19 disparities across racial and ethnic groups. OBJECTIVE: To use census tract-level data to investigate neighborhood-level factors contributing to racial and ethnic group-specific COVID-19 case rates in California. DESIGN: Quasi-Poisson generalized linear models were used to identify neighborhood-level factors associated with COVID-19 cases. In separate sequential models for Hispanic, Black, and Asian, we characterized the associations between neighborhood factors on neighborhood COVID-19 cases. Subanalyses were conducted on neighborhoods with majority Hispanic, Black, and Asian residents to identify factors that might be unique to these neighborhoods. Geographically weighted regression using a quasi-Poisson model was conducted to identify regional differences. MAIN MEASURES: All COVID-19 cases and tests reported through January 31, 2021, to the California Department of Public Health. Neighborhood-level data from census tracts were obtained from American Community Survey 5-year estimates (2015-2019), United States Census (2010), and United States Department of Housing and Urban Development. KEY RESULTS: The neighborhood factors associated with COVID-19 case rate were racial and ethnic composition, age, limited English proficiency (LEP), income, household size, and population density. LEP had the largest influence on the positive association between proportion of Hispanic residents and COVID-19 cases (- 2.1% change). This was also true for proportion of Asian residents (- 1.8% change), but not for the proportion of Black residents (- 0.1% change). The influence of LEP was strongest in areas of the Bay Area, Los Angeles, and San Diego. CONCLUSION: Neighborhood-level contextual drivers of COVID-19 burden differ across racial and ethnic groups.

Adenoma Detection Rate and Clinical Characteristics Influence Advanced Neoplasia Risk After Colorectal Polypectomy.

BACKGROUND AND AIMS: Postpolypectomy risk stratification for subsequent metachronous advanced neoplasia (MAN) is imprecise and does not account for colonoscopist adenoma detection rate (ADR). Our aim was to assess association of ADR with MAN and create a prediction model for postpolypectomy risk stratification incorporating ADR and other factors. METHODS: We conducted a retrospective cohort study of individuals with baseline polypectomy and subsequent surveillance colonoscopy from 2004 to 2016 within the U.S. Department of Veterans Affairs (VA). Clinical factors, polyp findings, and baseline colonoscopist ADR were considered for the model. Model performance (sensitivity, specificity, and area under the curve) for identifying individuals with MAN was compared with 2020 U.S. Multi-Society Task Force on Colorectal Cancer (USMSTF) surveillance recommendations. RESULTS: A total of 30,897 individuals were randomly assigned 2:1 into independent model training and validation sets. Increasing age, male sex, diabetes, current smoking, adenoma number, polyp location, adenoma ≥10 mm or with tubulovillous/villous features, and decreasing colonoscopist ADR were independently associated with MAN. A range of 1.48- to 1.66-fold increased risk for MAN was observed for ADR in the lowest 3 quintiles (ADR <19.7%-39.3%) vs the highest quintile (ADR >47.0%). When the final model selected based on the training set was applied to the validation set, improved sensitivity and specificity over 2020 USMSTF risk stratification were achieved (P = .001), with an area under the curve of 0.62 (95% confidence interval, 0.60-0.64). CONCLUSIONS: Colonoscopist ADR is associated with MAN. Combining clinical factors and ADR for risk stratification has potential to improve postpolypectomy risk stratification. Improving ADR is likely to improve postpolypectomy outcomes.

Patient perspectives of prostate cancer screening vary by race following 2018 guideline changes.

BACKGROUND: The 2018 US Preventive Services Task Force guidelines recommend individualizing prostate cancer screening in 55- to 69-year-old men. Given the higher incidence of prostate cancer in African American (AA) compared to non-Hispanic White (NHW) men, this study compared reported rates of prostate-specific antigen (PSA) screening hypothesizing that it would not be commensurate with the relative risk between these two groups. METHODS: Using the 2020 Behavioral Risk Factor Surveillance System, we identified 43,685 men (40,301 NHW and 3384 AA) interviewed about PSA screening. RESULTS: AA men had an odds ratio (OR) of 0.80 (95% confidence interval [CI], 0.69-0.93; p = .004) of reporting PSA screening; sequentially correcting for access to care, smoking, and age had minimal effect on this finding, but when correcting for income significantly attenuated this difference (OR, 0.95; 95% CI, 0.81-1.12). Further adding education level eliminated the effect size of AA race entirely with OR, 0.99 (95% CI, 0.84-1.17; p = .91). Further analysis found significant interaction between education and race, with college-educated AA men having 1.42 OR of receiving screening compared to college-educated NHW men. CONCLUSIONS: Despite prostate cancer being more common and having higher population-level mortality in AA than NHW men, PSA screening and education patterns do not reflect this increased risk even when adjusting for health access disparities. The authors' findings of significant effect from both income and education suggest that systemic racism is an important factor in the observed difference in PSA screening between AA men and NHW men. LAY SUMMARY: In the United States, prostate cancer is more common in African American men New guidelines from 2018 encourage physicians to consider risk factors in deciding whether or not to recommend screening, but overall African American men continue to be screened at a lower rate than non-Hispanic White men This effect disappears when correcting for income and education level, suggesting that several factors including systemic racism, medical mistrust, and self-advocacy may impact this observed difference.

Thyroid hormone elicits intergenerational epigenetic effects on adult social behavior and fetal brain expression of autism susceptibility genes.

Genetic mutations identified in genome-wide association studies can only explain a small percentage of the cases of complex, highly heritable human conditions, including neurological and neurodevelopmental disorders. This suggests that intergenerational epigenetic effects, possibly triggered by environmental circumstances, may contribute to their etiology. We previously described altered DNA methylation signatures in the sperm of mice that experienced developmental overexposure to thyroid hormones as a result of a genetic defect in hormone clearance (DIO3 deficiency). Here we studied fetal brain gene expression and adult social behavior in genetically normal F2 generation descendants of overexposed mice. The brain of F2 generation E13.5 fetuses exhibited abnormal expression of genes associated with autism in humans, including Auts2, Disc1, Ldlr, Per2, Shank3, Oxtr, Igf1, Foxg1, Cd38, Grid2, Nrxn3, and Reln. These abnormal gene expression profiles differed depending on the sex of the exposed ancestor. In the three-chamber social box test, adult F2 generation males manifested significantly decreased interest in social interaction and social novelty, as revealed by decrease total time, distance traveled and time immobile in the area of interaction with novel strangers. F1 generation mice, compared to appropriate controls also exhibited altered profiles in fetal brain gene expression, although these profiles were substantially different to those in the F2 generation. Likewise adult F1 generation mice showed some abnormalities in social behavior that were sexually dimorphic and milder than those in F2 generation mice. Our results indicate that developmental overexposure to thyroid hormone causes intergenerational epigenetic effects impacting social behavior and the expression of autism-related genes during early brain development. Our results open the possibility that altered thyroid hormone states, by eliciting changes in the epigenetic information of the germ line, contribute to the susceptibility and the missing-but heriTables-etiology of complex neurodevelopmental conditions characterized by social deficits, including autism and schizophrenia.