Search

Compared with urban residents, rural Americans have seen slower declines in cancer deaths, have lower incidence but higher death rates from cancers that can be prevented through screening, have lower screening rates, are more likely to present with later-stage cancers, and have poorer cancer outcomes and lower survival. Rural health provider shortages and lack of cancer services may explain some disparities. The literature was reviewed to identify factors contributing to rural health care capacity shortages and propose policy recommendations for improving rural cancer care. Uncompensated care, unfavorable payer mix, and low patient volume impede rural physician recruitment and retainment. Students from rural areas are more likely to practice there but are less likely to attend medical school because of lower graduation rates, grades, and Medical College Admission Test (MCAT) scores versus urban students. The cancer care infrastructure is costly and financially challenging in rural areas with high proportions of uninsured and publicly insured patients. A lack of data on oncology providers and equipment impedes coordinated efforts to address rural shortages. Graduate Medical Education funding greatly favors large, urban, tertiary care teaching hospitals over residency training in rural, critical access and community-based hospitals and clinics. Policies have the potential to transform rural health care. This includes increasing advanced practice provider postgraduate oncology training opportunities and expanding the scope of practice; improving health workforce and services data collection and aggregation; transforming graduate medical education subsidies to support rural student recruitment and rural training opportunities; and expanding federal and state financial incentives and payments to support the rural cancer infrastructure.

To describe characteristics of people who experience changes to their menstrual cycle following COVID-19 vaccination.Longitudinal study SUBJECTS: We recruited a volunteer sample with and without a history of SARS-CoV-2 infection who enrolled in the Arizona COVID-19 Cohort (CoVHORT) Study and consented to participate in a Reproductive Sub-Cohort who were pre-menopausal, not currently pregnant, and received a COVID-19 vaccine in 2021 (n=545).Demographic and reproductive characteristics were collected via self-report.Information on self-reported changes to the menstrual cycle following COVID-19 vaccination were collected from May-December 2021. We looked at demographic and reproductive characteristics as predictors of menstrual cycle change.The majority of our vaccinated sample received the Pfizer-BioNTech vaccine (58%), were 26-35 years old (51%), non-Hispanic (84%), and white (88%). Approximately 25% of vaccinated participants reported a change in their menstrual cycle following vaccination; the majority reported changes following their second dose (56%) as compared to their first (18%) and third dose (14%). The most common changes reported were irregular menstruation (43%), increase in premenstrual symptoms (34%), increase in menstrual pain or cramps (30%), and abnormally heavy or prolonged bleeding (31%). High self-reported perceived stress compared to low perceived stress (OR=2.22; 95% CI 1.12-4.37) and greater BMI (OR=1.04; 95% CI 1.00-1.07) was associated with greater odds of experiencing a change to the menstrual cycle following vaccination. Participants who had a history of SARS-CoV-2 infection were less likely to report changes to their menstrual cycle after vaccination compared to participants with no history of SARS-CoV-2 infection (OR=0.58; 95% CI 0.32-1.04).Among vaccinated participants, approximately 25% reported predominantly temporary changes to the menstrual cycle, however we are unable to determine whether these changes are due to normal cycle variability. The COVID-19 vaccines have been shown to be safe and effective for everyone, including pregnant people and people trying to conceive; these findings should not discourage vaccination.

Genetic variants related to colorectal adenoma may help identify those who are at highest risk of colorectal cancer development or illuminate potential chemopreventive strategies. The purpose of this genome-wide association study was to identify genetic variants that are associated with risk of developing a metachronous colorectal adenoma among 1,215 study participants of European descent from the Selenium Trial. Associations of variants were assessed with logistic regression analyses and validated in an independent case-control study population of 1,491 participants from the Colorectal Cancer Study of Austria (CORSA). No statistically significant genome-wide associations between any variant and metachronous adenoma were identified after correction for multiple comparisons. However, an intron variant of

Supplementary Table 1 from Genetic Variation in the Vitamin D Receptor (VDR) and the Vitamin D–Binding Protein (GC) and Risk for Colorectal Cancer: Results from the Colon Cancer Family Registry

Epidemiologic evidence supports a role for vitamin D in colorectal cancer (CRC) risk. Variants in vitamin D–related genes might modify the association between vitamin D levels and CRC risk. In this analysis, we did a comprehensive evaluation of common variants in the vitamin D receptor (VDR) and the vitamin D–binding protein (GC; group-specific component) genes using a population-based case–unaffected sibling control design that included 1,750 sibships recruited into the Colon Cancer Family Registry. We also evaluated whether any associations differed by calcium supplement use, family history of CRC, or tumor characteristics. Heterogeneity by calcium and vitamin D intake was evaluated for a subset of 585 cases and 837 sibling controls who completed a detailed food frequency questionnaire. Age- and sex-adjusted associations were estimated using conditional logistic regression. Overall, we did not find evidence for an association between any single-nucleotide polymorphism (SNP) in VDR or GC and risk for CRC (range of unadjusted P values 0.01-0.98 for VDR and 0.07-0.95 for GC). None of these associations was significant after adjustment for multiple comparisons. We also found no evidence that calcium or vitamin D intake (food and supplement) from the food frequency questionnaire modified the association estimates between VDR and GC SNPs and CRC. We did observe associations between SNPs in GC and microsatellite unstable CRC, although these results should be confirmed in additional studies. Overall, our results do not provide evidence for a role of common genetic variants in VDR or GC in susceptibility to CRC. Cancer Epidemiol Biomarkers Prev; 19(2); 525–36

Supplementary Tables 1-2 from Genetic Polymorphisms in Vitamin D Receptor VDR/RXRA Influence the Likelihood of Colon Adenoma Recurrence

Purpose: In the United States, Hispanics are more likely to be diagnosed with cervical cancer compared to Non-Hispanic Whites. Annually, 250,000 to 1 million women are diagnosed with a precursor to CC. The aim of this study was to assess whether Hispanics have a higher prevalence of cervical dysplasia compared to Non-Hispanics Whites among a population of low-income women. Patients and Methods: We analyzed the results of 10,911 cervical cytology tests administered between 2003 and 2016 that were funded through the Center for Disease Control and Prevention's (CDC) program for low-income, uninsured women entitled the National Breast and Cervical Cancer Early Detection Program (NBCCEDP). In the state of Arizona, the program is called the Well Women HealthCheck Program (WWHP). Logistic regression was used to identify increased risk of dysplasia, including low-grade squamous intraepithelial lesions (LSIL) and high-grade squamous intraepithelial lesions (HSIL/ICC), and multinomial logistic regression was used to assess increased likelihood for LSIL and HSIL/ICC as separate categories. Results: In the crude analysis, Hispanic ethnicity was modestly associated with higher prevalence of LSIL (odds ratio (OR)=1.39, 95% CI=1.01-1.91), but this association was not statistically significant after adjusting for confounders. However, in the final models, lower income was independently associated with LSIL (adjusted odds ratio [aOR]=1.55, 95% CI=1.30-1.44), while smoking (aOR=2.88, 95% CI=1.21-6.84) and no history of Pap test within five years (aOR=3.54, 95% CI=1.61-6.99) were independently associated with HSIL. Conclusion: After adjusting for confounding in a sample of low-income women with comparable Pap screening rates, ethnicity was not associated with greater prevalence of abnormal pap smears. However, other variables were independently associated with LSIL and HSIL. The higher proportion of LSIL cases among lower income individuals compared to those with higher incomes, and the higher proportion of HSIL cases observed among those screened least regularly stresses the importance of programs like WWHP: programs that target low-income, uninsured women. These programs help save lives.

IntroductionTreatment delays are significantly associated with increased mortality risk among adult cancer patients; however, factors associated with these delays have not been robustly evaluated. This review and meta-analysis will evaluate factors associated with treatment delays among patients with five common cancers.Methods and analysisScientific databases including Ovid MEDLINE, Elsevier Embase, EBSCOhost CINAHL Plus Full Text, Elsevier Scopus and ProQuest Dissertations and Theses Global will be searched to identify relevant articles published between January 2000 and October 2021. Research articles published in the USA evaluating factors associated with treatment delay among breast, lung, prostate, cervical or colorectal adult cancer patients will be included. The primary outcome of the meta-analysis will be the pooled adjusted and unadjusted odds of treatment delay for patient, disease, provider and system-level factors defined according to specified time intervals. The secondary outcomes will be mean or median treatment delay for each cancer site according to first treatment and the influence of factors on the pooled mean treatment delay for each cancer site (via meta-regression analyses). Results from qualitative and mixed-methods studies will be narratively synthesised. Three reviewers will independently screen records generated from the search and two reviewers will independently extract data following a consensus agreement. Statistical heterogeneity will be assessed with a standard I2 test and funnel plots will be conducted to evaluate publication bias. Risk of bias will be assessed independently by two authors using validated tools according to the article’s study design.Ethics and disseminationFormal ethical approval is not required because the work is being carried out on publicly accessible studies. The findings of this review will be disseminated through a peer-reviewed scientific journal, academic conferences, social media, and key stakeholders.PROSPERO registration numberCRD42021293131.

PURPOSE: The aim of this study was to describe diet and physical activity (PA) behaviors and health beliefs among cancer survivors and identify potential differences between adolescent and young adult (AYA) and adult/older cancer survivors. METHODS: Cancer survivors (n = 1864) participating in the Health Information National Trends Survey (HINTS) provided responses regarding diet and PA and selected health beliefs related to general health and cancer (self-efficacy, attitudinal belief, normative belief, risk belief, intention, and self-regulation). Health belief associations with diet and PA were assessed using adjusted logistic regression models, and multiple linear regression was used for a computed Modified American Cancer Society Adherence score (0–10, higher score indicates higher adherence to recommendations); age at diagnosis was evaluated as a potential effect modifier. RESULTS: Health behaviors between AYA and adult/older were not significantly different; a greater percent of AYA met fruit and resistance PA recommendations. Higher health self-efficacy was associated with meeting aerobic PA recommendations (odds ratio [OR]: 1.71; confidence interval [95% CI]: 1.13–2.60; p = 0.01). Higher intention was inversely related to meeting vegetable recommendation (OR: 0.58; 95% CI: 0.35–0.97; p = 0.04). Self-regulation was associated with higher odds of meeting each recommendation. Self-efficacy and self-regulation were associated with greater adherence (β = 0.52 ± 0.16, p = 0.001; β = 1.21 ± 0.24, p

Background Although chronic kidney disease (CKD) affects 15% of the United States (US) population, Methods Data from the 1999–2014 National Health and Nutrition Examination Survey (NHANES) were used (n = 38 474); response rate > 70%. CKD self-report and lab-confirmed CKD were used to assess CKD unawareness. Adjusted logistic regression models examined association between unawareness and patient characteristics. Results In individuals with lab-confirmed CKD (n = 7137, 14.3%), 91.5% answered ‘no’ to self-report question; in those without CKD, 1.1% answered ‘yes’ to self-report question. In those with lab-confirmed CKD, in the adjusted models, increased age [odds ratio (ORs), 1.03 (95%CI, 1.02–1.04)] and female sex [OR, 1.37 (95%CI, 1.08–1.72)] were statistically significantly associated with greater odds of being unaware of CKD. Conclusion These findings demonstrated high unawareness of disease status as there was a discrepancy between respondents’ self-reported CKD diagnosis and lab-confirmed CKD. Older individuals and women may be more unaware of their CKD; these groups should be queried about reasons for increased unawareness.

BACKGROUND: Selenium (Se) is a trace element that has been linked to many health conditions. Genome-wide association studies (GWAS) have identified variants for blood and toenail Se levels, but no GWAS has been conducted to date on responses to Se supplementation. OBJECTIVES: A GWAS was performed to identify the single nucleotide polymorphisms (SNPs) associated with changes in Se concentrations after 1 year of supplementation. A GWAS of basal plasma Se concentrations at study entry was conducted to evaluate whether SNPs for Se responses overlap with SNPs for basal Se levels. METHODS: A total of 428 participants aged 40–80 years of European descent from the Selenium and Celecoxib Trial (Sel/Cel Trial) who received daily supplementation with 200 µg of selenized yeast were included for the GWAS of responses to supplementation. Plasma Se concentrations were measured from blood samples collected at the time of recruitment and after 1 year of supplementation. Linear regression analyses were performed to assess the relationship between each SNP and changes in Se concentrations. We further examined whether the identified SNPs overlapped with those related to basal Se concentrations. RESULTS: No SNP was significantly associated with changes in Se concentration at a genome-wide significance level. However, rs56856693, located upstream of the NEK6, was nominally associated with changes in Se concentrations after supplementation (P = 4.41 × 10(−7)), as were 2 additional SNPs, rs11960388 and rs6887869, located in the dimethylglycine dehydrogenase (DMGDH)/betaine-homocysteine S-methyltransferase (BHMT) region (P = 0.01). Alleles of 2 SNPs in the DMGDH/BHMT region associated with greater increases in Se concentrations after supplementation were also strongly associated with higher basal Se concentrations (P = 8.67 × 10(−8)). CONCLUSIONS: This first GWAS of responses to Se supplementation in participants of European descent from the Sel/Cel Trial suggests that SNPs in the NEK6 and DMGDH/BHMT regions influence responses to supplementation.

The rates of early-onset colorectal cancer (EO-CRC) have been rising by 0.5% to 2.4% annually for three decades, accounting for an estimated 12% of all colorectal cancer diagnosed in the United States in 2020. Enhancing the rigor and comprehensiveness of the epidemiology in terms of the exposures and prognostic biomarkers is essential if we are to modify risk factors and underlying mechanisms, ultimately arresting this unduly trend. This commentary serves to describe the disease trend, postulate underlying risk factors and mechanisms driving disease incidence, and proposes a call to action for cancer epidemiologists to promote increased and timely opportunities to intervene on this trend.

Serotonin toxicity (ST) is a serious clinical entity caused by drug-induced serotonin excess in the central nervous system. Animal studies and some human data indicate that activation of specific serotonin receptor subtypes, namely 5-HT1A and 5-HT2A, are involved in ST pathophysiology, suggesting that serotonin antagonists could be used to treat ST. However, to date, high-quality evidence for the clinical utility of the most commonly employed serotonin antagonist, cyproheptadine, is lacking. This systematic review provides a clinical update on the evidence regarding use cyproheptadine for treating ST and compiles cyproheptadine treatment recommendations from recent review articles. Published articles concerning the use of cyproheptadine for treating ST are exclusively case reports and case series (n = 151); most provide very low-quality evidence (i.e., grade D, n = 148) and the remaining few provide low-quality evidence (i.e., grade C, n = 3). Most recent review articles (n = 18) acknowledge this low level of evidence and propose cyproheptadine as an optional treatment, whereas others recommend its use in the clinical setting. Although ST has been recognized as a clinical entity for decades, rigorous trials demonstrating the therapeutic efficacy of cyproheptadine are lacking, warranting large-scale prospective human trials of antiserotonergic agents using a coordinated multicenter approach.

Adolescent and young adult (AYA) cancer survivors, here defined as individuals diagnosed with cancer between 15 and 39 years of age, are at high risk for adverse late-term metabolic effects of treatment through adulthood. Diet is a modifiable lifestyle behavior that may improve metabolic health outcomes in AYA cancer survivors. However, the details of dietary interventions for this unique population remain largely undescribed. In this systematic review, we aim to synthesize the results of dietary interventions for adult AYA cancer survivors. Seven databases and clinical trial registries were searched in March 2019 for interventions targeting dietary behaviors in AYA cancer survivors (PROPSERO systematic review number: CRD42019126376). Descriptive statistics and a narrative synthesis were completed to detail intervention participants and components. After full text review of 233 studies, four studies met all inclusion criteria. All studies were heterogeneous for participant age, cancer type, and duration, and were designed for feasibility and preliminary efficacy. Included studies followed different dietary guidance; however, each resulted in a significant change on a primary outcome of either dietary quality or body composition. Three of the four studies included a theoretical framework, where self-efficacy was a central construct. Counseling, in person, telephone, or electronic, provided behavioral support. Results of this systematic review suggest high potential to change dietary behaviors in AYA, but interventions remain limited. AYA cancer survivors demonstrate unique physiological and psychosocial needs, and future interventions designed to address this care gap should be targeted for this population with consideration of social support, delivery mode, and individual tailoring.

IntroductionSub-Saharan Africa has the highest global incidence of cervical cancer. Cervical cancer is the most common cause of cancer morbidity and mortality among women in Zambia. HIV increases the risk for cervical cancer and with a national Zambian adult HIV prevalence of 16%, it is important to investigate the impact of HIV on the progression of cervical cancer. We measured differences in cervical cancer progression between HIV-positive and HIV-negative patients in Zambia.MethodsThis study included 577 stage I and II cervical cancer patients seen between January 2008 and December 2012 at the Cancer Diseases Hospital in Lusaka, Zambia. The inclusion criteria for records during the study period included known HIV status and FIGO stage I and II cervical cancer at initial date of registration in the Cancer Diseases Hospital. Medical records were abstracted for clinical and epidemiological data. Cancer databases were linked to the national HIV database to assess HIV status among cervical cancer patients. Logistic regression examined the association between HIV and progression, which was defined as metastatic or residual tumor after 3 months of initial treatment.ResultsA total of 2451 cervical cancer cases were identified, and after exclusion criteria were performed the final analysis population totaled 537 patients with stage I and II cervical cancer with known HIV status (224 HIV-positive and 313 HIV-negative). HIV-positive women were, on average, 10 years younger than HIV-negative women who had a median age of 42, ranging between 25 and 72. A total of 416 (77.5%) patients received external beam radiation, and only 249 (46.4%) patients received the recommended treatment of chemotherapy, external beam radiation, and brachytherapy. Most patients were stage II (85.7%) and had squamous cell carcinoma (74.7%). HIV-positive patients were more likely to receive lower doses of external beam radiation than HIV-negative patients (47% vs 37%; PConclusionThere was no significant impact on non-metastatic cervical cancer progression by HIV status among patients in Lusaka, Zambia. The high prevalence of HIV among cervical cancer patients suggest that HIV-positive patients should be a primary target group for HPV vaccinations, screening, and early detection.

Education intervention effectiveness to improve bed net care and repair knowledge or practices is unclear. To assess intervention effectiveness, we systematically reviewed eight peer-reviewed literature databases and 16 malaria organizations (PROSPERO protocol CRD42019123932) using pre-specified combinations of ‘education intervention’, ‘mosquito net’, and ‘malaria’ search terms. Data were abstracted for 29 of 43 studies meeting inclusion criteria, of which 16 studies included education as amain focus. Of these 16, there was evidence of intervention effectiveness among half of the studies, which reported improvements in knowledge or practices, while four had mixed results, and four had unclear results. Overall there is no clear conclusion regarding the effectiveness of education interventions to improve net care and repair, though some instructional methods suggest more success than others. Interventions used combinations of instructional methods; passive mass education (6), active mass education (12), and interpersonal methods (8). Interventions combining mass and interpersonal methods resulted in positive improvements (four positive, one mixed). We found no evidence that interventions grounded in health behavior theory achieved more positive results than those not grounded in theory, potentially because net care education was typically asecondary objective. Of 289 gray literature results, 286 (99%) were net distribution reports from Against Malaria Foundation describing 136 distributions; eighty of which (58.8%) mentioned no education related to net care and repair. We found lack of involvement of experts in education among included interventions. Involving trained instructors with expertise in education theory and instructional strategies may improve instruction quality to yield more effective interventions.

ObjectiveTo elucidate the symptoms of laboratory-confirmed COVID-19 cases as compared with laboratory-confirmed negative individuals and to the untested general population among all participants who reported symptoms within a large prospective cohort study.Setting and designThis work was conducted within the framework of the Arizona CoVHORT, a longitudinal prospective cohort study conducted among Arizona residents.ParticipantsEligible participants were any individual living in Arizona and were recruited from across Arizona via COVID-19 case investigations, participation in testing studies and a postcard mailing effort.Primary and secondary outcome measuresThe primary outcome measure was a comparison of the type and frequency of symptoms between COVID-19-positive cases, tested but negative individuals and the general untested population who reported experiencing symptoms consistent with COVID-19.ResultsOf the 1335 laboratory-confirmed COVID-19 cases, 180 (13.5%) reported having no symptoms. Of those that did report symptoms, the most commonly reported were fatigue (82.2%), headache (74.6%), aches, pains or sore muscles (66.3%), loss of taste or smell (62.8) and cough (61.9%). In adjusted logistic regression models, COVID-19-positive participants were more likely than negative participants to experience loss of taste and smell (OR 12.1; 95% CI 9.6 to 15.2), bone or nerve pain (OR 3.0; 95% CI 2.2 to 4.1), headache (OR 2.6; 95% CI 2.2 to 3.2), nausea (OR 2.4; 95% CI 1.9 to 3.1) or diarrhoea (OR 2.1; 95% CI 1.7 to 2.6). Fatigue (82.9) and headache (74.9) had the highest sensitivities among symptoms, while loss of taste or smell (87.2) and bone or nerve pain (92.9) had the high specificities among significant symptoms associated with COVID-19.ConclusionWhen comparing confirmed COVID-19 cases with either confirmed negative or untested participants, the pattern of symptoms that discriminates SARS-CoV-2 infection from those arising from other potential circulating pathogens may differ from general reports of symptoms among cases alone.

Oxylipins derived from arachidonic acid (ARA) have been implicated in the development of colorectal adenomas and colorectal cancer. The primary purpose of this work was to determine the relationship between plasma levels of oxylipins and colorectal adenoma characteristics at study entry, as well as with the development of a new adenoma during follow-up within a Phase III adenoma prevention clinical trial with selenium (Sel). Secondarily, we sought to determine whether the selenium intervention influenced plasma oxylipin levels. Four oxylipins were quantified in stored plasma samples from a subset of Sel study subjects (n = 256) at baseline and at 12-months. There were significantly lower odds of an advanced adenoma at baseline with higher prostaglandin E2 (PGE2), with an OR (95% CI) of 0.55 (0.33–0.92), and with 5-hydroxyeicosatetraenoic acid (5-HETE) ((0.53 (0.33–0.94)), and of a large adenoma with higher PGE2 ((0.52 (0.31–0.87)). In contrast, no associations were observed between any oxylipin and the development of a new adenoma during follow-up. Selenium supplementation was associated with a significantly smaller increase in 5-HETE after 12 months compared to the placebo, though no other results were statistically significant. The ARA-derived oxylipins may have a role in the progression of non-advanced adenoma to advanced, but not with the development of a new adenoma.

BackgroundHormone receptor (HR) testing was not available for tailoring treatment of breast cancer in Tanzania until 2015. The aim of this study was to compare effect of introducing HR testing on breast cancer treatment in Tanzania. MethodsThis retrospective study included 2 groups of breast cancer patients treated at Ocean Road Cancer Institute (ORCI) before introducing HR (2007-2009 and 2014 – 685 patients), and after HR introduction (2015-2017 –765 patients). Demographic, epidemiologic and clinical data were abstracted from the medical records of patients. Chi-Square and Wilcoxon rank sum analyses were used to compare treatment in the two periods. ResultsStage at diagnosis did not differ significantly by ER status (12.4% vs. 7.3%, stages I and II combined, 13.4% vs. 19.3% for stage III, and 30.7% vs 37.0% for stage IV with p-values of 0.08, 0.21, and 0.44, respectively). The proportion of patients who received both neoadjuvant chemotherapy alone (29.2% vs 28.1%) and adjuvant chemotherapy (53.5% vs 48.4%) did not differ significantly by ER status, (p=0.64 and p=0.29, respectively). After implementing ER testing, the proportion of patients who did not receive radiotherapy differed by ER status (43.6% vs 32.8%, p=0.04). Furthermore, approximately 13% of ER-negative patients received endocrine therapy, compared to 60% of ER positive patients (p < 0.0001).DiscussionThese finding suggest that there have been significant changes in breast cancer treatment practices since the introduction of hormone receptor testing. However, further research is needed to determine how hormone receptor status can be used to optimize standardized treatment protocols for patients diagnosed with breast cancer in Tanzania and other low-income countries that are taking steps to improve their breast cancer management practices and protocols.

Introduction: While cancer deaths have decreased nationally, declines have been much slower in rural areas than in urban areas. Previous studies on rural cancer service capacity are limited to specific points along the cancer care continuum (eg screening, diagnosis or treatment) and require updating to capture the current rural health landscape since implementation of the 2010 Affordable Care Act in the USA. The association between current rural cancer service capacity across the cancer care continuum and cancer incidence and death is unclear. This cross-sectional study explored the association between breast cancer service capacity and incidence and mortality in Arizona's low populous counties. Methods: To measure county-level cancer capacity, clinical organizations operating within low populous areas of Arizona were surveyed to assess on-site breast cancer services provided (screening, diagnosis and treatment) and number of healthcare providers were pulled from Centers for Medicare and Medicaid Services National Provider Identifier database. The number of clinical sites and healthcare providers were converted to county-level per capita rates. Rural-Urban Continuum codes were used to designate rural or urban county status. Age-adjusted county-level breast cancer incidence and death rates from 2010 to 2016 were obtained from the Arizona Department of Health Services, Arizona Cancer Registry. Descriptive statistics were used to summarize the results. Multivariate regression was used to evaluate the association between cancer service capacity and incidence and mortality in 13 out of Arizona's 15 counties. Results: Rural counties had more per capita clinical sites (20.4) than urban counties (8.9) (p=0.02). Urban counties had more per capita pathologists (1.0) than rural counties (0) (p≤0.01). In addition to zero pathologists, rural counties had zero medical oncologists. Rural county status was associated with a decrease in breast cancer incidence (β=-20.1, 95% confidence interval: -37.2-3.1). Conclusion: While Arizona's sparsely populated rural counties may have more physical infrastructure per capita, these services are dispersed over vast geographic areas. They lack specialists providing cancer services. Non-physician clinical providers may be more prevalent in rural areas and represent opportunities for improving access to cancer preventive services and care. Compared to urban counties, rural county status was associated with lower detected breast cancer incidence rates although there were no statistically significant differences in breast cancer mortality. Other factors may contribute to rural-urban differences in breast cancer incidence. Future research should explore these factors and the association between cancer capacity and local resources because the use of county-level data represents a challenge in Arizona, where counties average over 19 425 km2 (7500 square miles).

Background Insecticide-treated nets (ITNs) and long-lasting insecticidal nets (LLINs) are effective for malaria prevention and are designed to provide nearly 5 years of mosquito protection. However, many ITNs and LLINs become damaged and ineffective for mosquito bite prevention within 1 to 2 years in field conditions. Non-adherence to recommended bed net care and repair practices may partially explain this shortened net longevity. Methods Using data from a cross-sectional study, a net care adherence score was developed and adherence to net care practices described from two regions of western Kenya. Relationships between attitudes and environmental factors that influence net longevity were measured with adherence to bed net care practices. Results While overall care practices are highly adherent particularly in the highlands, practices related to daily storage, washing frequency, and drying location need improvement in the lowlands. Seventy-seven percent of nets in the lowlands were washed

Background: Mexican Americans (MAs) have the highest rates of liver steatosis, nonalcoholic fatty liver disease, and liver cancer compared to other Hispanic subpopulations, non-Hispanic Whites, and non-Hispanic Blacks. While some diet patterns have been identified to increase or decrease risk of liver steatosis and fibrosis, no research to our knowledge has identified diet patterns associated with these outcomes in MAs. The purpose of this study was to examine associations between dietary patterns derived from factor analysis and liver steatosis and fibrosis in a nationally representative sample of MAs. Methods: We conducted a cross-sectional analysis of participant data from the National Health and Nutrition Examination Survey 2017-2018. Participants were adults who identified as MA who were not pregnant or breastfeeding and had no previous diagnosis of hepatitis A or B, cirrhosis, or liver cancer. Dietary patterns were derived by exploratory factor analysis of 24-hr dietary recall data. Individuals who completed only one recall, had unreliable dietary data, or reported an average caloric intake < 500 kcals/day or > 4,000 kcals/day were excluded. Elastography measurements were obtained from eligible participants in a fasting state using the Fibroscan® which provided measures of liver steatosis as controlled attenuation parameter and liver stiffness, a validated proxy for fibrosis. The associations of each derived dietary pattern with liver steatosis and fibrosis were evaluated in multivariate linear regression models controlling for body mass index (BMI), sex, age, average total caloric intake, sedentary time, household income, diabetes status, and smoking status. Results: The final analytic sample consisted of 633 MA adults with a mean age of 37.7 ± 0.3 years and mean BMI of 31.0 ± 1.1 kg/m2. Five factors (i.e. diet patterns) were derived accounting for 86% of the variation prior to rotation. Factor 4, characterized by relatively high intake of nuts, seeds, and oils was significantly associated with decreased levels of liver steatosis in two of the three models but not the fully-adjusted model. Factor 4 was also significantly associated with decreased fibrosis in all three models, including the fully-adjusted model (p=0.05). Factor 2, characterized by relatively high intake of milk and dairy, was significantly associated with increased levels of liver steatosis in two of the three models, including the fully-adjusted model (p=0.03). Conclusion: In a large, nationally representative sample of MA adults, we identified diet patterns associated with levels of liver fibrosis and steatosis in an exploratory analysis. Future research should investigate the association of dietary patterns in larger samples to inform interventions to reduce liver disease risk in MAs. Citation Format: Kristin E. Morrill, Melissa Lopez-Pentecost, Joel Parker, David O. Garcia, Elizabeth T. Jacobs. Association of dietary patterns and liver steatosis and fibrosis among Mexican Americans in NHANES 2017-2018 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5955.

Clinical presentation, outcomes, and duration of COVID-19 has ranged dramatically. While some individuals recover quickly, others suffer from persistent symptoms, collectively known as long COVID, or post-acute sequelae of SARS-CoV-2 (PASC). Most PASC research has focused on hospitalized COVID-19 patients with moderate to severe disease. We used data from a diverse population-based cohort of Arizonans to estimate prevalence of PASC, defined as experiencing at least one symptom 30 days or longer, and prevalence of individual symptoms. There were 303 non-hospitalized individuals with a positive lab-confirmed COVID-19 test who were followed for a median of 61 days (range 30–250). COVID-19 positive participants were mostly female (70%), non-Hispanic white (68%), and on average 44 years old. Prevalence of PASC at 30 days post-infection was 68.7% (95% confidence interval: 63.4, 73.9). The most common symptoms were fatigue (37.5%), shortness-of-breath (37.5%), brain fog (30.8%), and stress/anxiety (30.8%). The median number of symptoms was 3 (range 1–20). Amongst 157 participants with longer follow-up (≥60 days), PASC prevalence was 77.1%.

Accurate diagnosis of potential SARS-CoV-2 infections by symptoms is one strategy for continuing global surveillance, particularly in low-resource communities. We conducted a prospective, population-based cohort study, the Arizona CoVHORT, among Arizona residents to elucidate the symptom profile of laboratory-confirmed COVID-19 participants(16.2%) compared to laboratory-confirmed negative(22.4%) and untested general population participants(61.4%). Among the 1514 study participants, those who were COVID-19 positive were more likely to be Hispanic(33.5%) and more likely to report obesity > 30 kg/m2(34.7%) compared to COVID-19 negative participants(19.2%; 31.0%) and untested CoVHORT participants(13.8%; 23.8%). Of the 245 laboratory-confirmed COVID-19 cases, 15.0% reported having had no symptoms. Of those that did report symptoms, the most commonly-reported first symptoms were sore throat(19.0%), headache(15.5%), cough(12.7%), runny nose/cold-like symptoms(12.1%), and fatigue(12.0%). In adjusted logistic regression models, COVID-19 positive participants were more likely than negative participants to experience loss of taste and smell(OR:35.7; 95% CI 18.4-69.5); bone or nerve pain(OR:17.9; 95% CI 6.7-47.4), vomiting(OR:10.8; 95% CI 3.1-37.5), nausea(OR:10.5; 95% CI 5.5-19.9), and headache(OR:8.4; 95% CI 5.6-12.8). When comparing confirmed COVID-19 cases with confirmed negative or untested participants, the pattern of symptoms that discriminates SARS-CoV-2 infection from those arising from other potential circulating pathogens may differ from general reports of symptoms among cases alone.

Female firefighters have occupational exposures which may negatively impact their reproductive health. Anti-müllerian hormone (AMH) is a clinical marker of ovarian reserve. We investigated whether AMH levels differed in female firefighters compared to non-firefighters and whether there was a dose-dependent relationship between years of firefighting and AMH levels. Female firefighters from a pre-existing cohort completed a cross-sectional survey regarding their occupational and health history and were asked to recruit a non-firefighter friend or relative. All participants provided a dried blood spot (DBS) for AMH analysis. Linear regression was used to assess the relationship between firefighting status and AMH levels. Among firefighters, the influence of firefighting-related exposures was evaluated. Firefighters (n = 106) and non-firefighters (n = 58) had similar age and BMI. Firefighters had a lower mean AMH compared to non-firefighters (2.93 ng/mL vs. 4.37 ng/mL). In multivariable adjusted models, firefighters had a 33% lower AMH value than non-firefighters (−33.38%∆ (95% CI: −54.97, −1.43)). Years of firefighting was not associated with a decrease in AMH. Firefighters in this study had lower AMH levels than non-firefighters. More research is needed to understand the mechanisms by which firefighting could reduce AMH and affect fertility.

Prior work has shown that higher circulating concentrations of fibroblast growth factor-21 (FGF-21) are associated with an increased likelihood of developing colorectal cancer. We conducted a prospective study to assess the relationship between circulating FGF-21 and odds of developing early neoplastic lesions in the colorectum.A total of 94 study participants were included from the ursodeoxycholic acid (UDCA) trial, a phase III, randomized, double-blind, placebo-controlled clinical trial of the effect of 8-10 mg/kg of body weight UDCA vs. placebo. Logistic regression analyses were conducted to evaluate the association between baseline FGF-21 concentrations and odds of developing a metachronous adenoma.Of the characteristics compared across tertiles of FGF-21 concentrations, including age, race, sex, BMI, and other variables, only a previous personal history of colorectal polyps prior to entry into the UDCA trial was statistically significantly related to FGF-21 levels, with a proportion of 26.7%, 56.7%, and 50.0% across the first, second, and third tertiles, respectively (p 0.05). Higher circulating concentrations of FGF-21 were statistically significantly associated with greater odds of developing a metachronous colorectal adenoma. After adjusting for potential confounders and when compared with the lowest tertile of FGF-21, the adjusted ORs (95% CIs) for metachronous colorectal adenoma in the second and third tertiles were 4.72 (95% CI, 1.42-15.72) and 3.82 (95% CI, 1.15-12.68), respectively (p trend 0.05).Our results reveal for the first time that, in addition to a recently discovered association with colorectal cancer, circulating FGF-21 concentrations are significantly and directly associated with odds of developing metachronous colorectal adenoma.

Background Alternative long-lasting insecticidal net (LLIN) use for purposes other than sleeping protection from mosquitoes is widely debated as a limitation to successful malaria control efforts, yet rarely rigorously studied. Methods A cross-sectional survey of 1217 households in an epidemic highland site and an endemic lowland site in western Kenya collected information on alternative use in three ways: direct observations, participant self-report, and participant reporting of community-level practices. LLIN misuse was defined as use of an intact net for alternative purposes and repurposing as alternatively using an old or damaged net. Associations between households with observed repurposed nets and universal access and household net use were examined. Results Households describe repurposing nets when they are torn and/or old. Repurposed nets were observed in 8.1% (52/643) highlands households and 33.0% (184/574) lowlands households. Repurposed nets served as chicken coops (33% highlands, 20% lowlands), fences (37% highlands, 25% lowlands), tree covers (22% lowlands), curtains (3% highlands), covering bathrooms (1.5% highlands, 9% lowlands), and washing sponges (13% lowlands). No association was found between repurposing and universal access or household net use. Misuse was rare. Of 379 repurposed nets, 4 (1.06%) were in good condition with no holes. Of 1,758 active nets, 13 (0.74%) were misused. Conclusions Alternative net use in this study involved repurposing rather than misuse. Repurposing was not detrimental to malaria prevention efforts in these communities. Standardized measurement of alternative net use should be used to better understand the practice and its potential impact on the success of malaria interventions.

BACKGROUND: Vitamin D deficiency and insufficiency are associated with serious sequelae in childhood cancer survivors. However, data on vitamin D deficiency in children with newly diagnosed cancer are scarce and the role of sociodemographic factors and vitamin D supplementation is largely unknown. METHODS: We assessed vitamin D status and its socio-demographic and clinical correlates in 163 children with newly diagnosed cancer, using 25-hydroxy vitamin D (25(OH)D) concentrations and assessed longitudinal changes following vitamin D supplementation. RESULTS: Sixty-five percent of the patients with newly diagnosed cancer had low 25(OH)D concentrations. Fifty-two patients (32%) were vitamin D deficient (≤20 ng/mL 25(OH)D concentration), and 53(33%) were insufficient (21–29 ng/mL 25(OH)D concentration). Age over 10 (P=0.019), Hispanic ethnicity (P=0.002), and female sex (P=0.008) were significantly associated with lower 25(OH)D concentration at diagnosis. Vitamin D supplementation resulted in significant increase in 25(OH)D concentrations (P

Dairy products have been a key component of dietary guidance in the United States for more than 100 years. In light of major advances in the understanding of dietary intake and metabolism, the aim of this review was to examine whether dairy should remain a single commodity in federal guidance. Considerations include recognizing that a substantial proportion of the world’s adult population (65%–70%) exhibits lactase nonpersistence, a reduced ability to metabolize lactose to glucose and galactose. Shifts in the US population, including a greater proportion of African Americans and Asians, are of key importance because several studies have shown a markedly higher prevalence of lactase nonpersistence and, consequently, a lower dairy intake among these groups. While cow’s milk alternatives are available, families who use them will pay up to an additional $1400 per year compared with those who are able to consume dairy products. Dietary guidance also contains downstream effects for government assistance, such as the US Department of Agriculture’s National School Lunch Program and School Breakfast Program. For reasons like these, Canada has recently removed dairy as a separate food group in national dietary guidance. The results of the present review suggest that consideration of this modification when developing population-level guidelines in the United States is warranted.

Little is known about the relationship between having a first-degree relative (FDR) with colorectal cancer (CRC) and risk for metachronous colorectal adenoma (CRA) following polypectomy. We pooled data from seven prospective studies of 7697 patients with previously resected CRAs to quantify the relationship between having a FDR with CRC and risk for metachronous adenoma. Compared with having no family history of CRC, a positive family history in any FDR was significantly associated with increased odds of developing any metachronous CRA (OR = 1.14; 95% CI = 1.01–1.29). Higher odds of CRA were observed among individuals with an affected mother (OR = 1.27; 95% CI = 1.05–1.53) or sibling (OR = 1.34; 95% CI = 1.11–1.62) as compared with those without, whereas no association was shown for individuals with an affected father. Odds of having a metachronous CRA increased with number of affected FDRs, with ORs (95% CIs) of 1.07 (0.93–1.23) for one relative and 1.39 (1.02–1.91) for two or more. Younger age of diagnosis of a sibling was associated with higher odds of metachronous CRA, with ORs (95% CIs) of 1.66 (1.08–2.56) for diagnosis at 65 years (p-trend = 0.008). Although limited by sample size, results for advanced metachronous CRA were similar to those for any metachronous CRA. A family history of CRC is related to a modestly increased odds of metachronous CRA. Future research should explore whether having a FDR with CRC, particularly at a young age, should have a role in risk stratification for surveillance colonoscopy.

Objectives: Firefighters have elevated cancer incidence and mortality rates. MicroRNAs play prominent roles in carcinogenesis, but have not been previously evaluated in firefighters. Methods: Blood from 52 incumbent and 45 new recruit nonsmoking firefighters was analyzed for microRNA expression, and the results adjusted for age, obesity, ethnicity, and multiple comparisons. Results: Nine microRNAs were identified with at least a 1.5-fold significant difference between groups. All six microRNAs with decreased expression in incumbent firefighters have been reported to have tumor suppressor activity or are associated with cancer survival, and two of the three microRNAs with increased expression in incumbent firefighters have activities consistent with cancer promotion, with the remaining microRNA associated with neurological disease. Conclusion: Incumbent firefighters showed differential microRNA expression compared with new recruits, providing potential mechanisms for increased cancer risk in firefighters.

At a storefront museum approximately 25 miles southeast of Pittsburgh, Pennsylvania, a sign reads, “Clean Air Started Here.” This is not hyperbole. At the end of October 1948, the communities of Donora and Webster in Pennsylvania were visited by a smog that changed the face of environmental protection in the United States. Conservative estimates showed that 20 individuals died, while an additional 5900—43% of the population of Donora—were affected by the smog. This event led to the first large-scale epidemiological investigation of an environmental health disaster in the United States. Questions remain about the long-term effects of the smog, because higher rates of cardiovascular disease and cancer than were expected were observed in the region in the decade following the smog. Recent work has suggested that environmental contaminants from a bygone era in Donora might have an impact even today. In addition, reports regarding air pollution have indicated that levels of pollutants similar to those estimated to have occurred in Donora are currently present in some rapidly industrializing regions of China and India. Seventy years after the smog, this event still resonates.

The hormonal metabolite of vitamin D, 1,25-dihydroxyvitamin D3 (1,25D), binds to the vitamin D receptor (VDR) and promotes heterodimerization of VDR with a retinoid-X-receptor (RXR) to genomically regulate diverse cellular processes. Herein, it is revealed for the first time that VDR is post-translationally acetylated, and that VDR immunoprecipitated from human embryonic kidney (HEK293) cells displays a dramatic decrease in acetylated receptor in the presence of 1,25D-ligand, sirtuin-1 (SIRT1) deacetylase, or the resveratrol activator of SIRT1. To elucidate the functional significance of VDR deacetylation, vitamin-d-responsive-element (VDRE)-based transcriptional assays were performed to determine if deacetylase overexpression affects VDR/VDRE-driven transcription. In HEK293 kidney and TE85 bone cells, co-transfection of low amounts (1-5ng) of a SIRT1-expression vector elicits a reproducible and statistically significant enhancement (1.3- to 2.6-fold) in transcription mediated by VDREs from the CYP3A4 and cyp24a1 genes, where the magnitude of response to 1,25D-ligand is 6- to 30-fold. Inhibition of SIRT1 via EX-527, or utilization of a SIRT1 loss-of-function mutant (H363Y), resulted in abrogation of SIRT1-mediated VDR potentiation. Studies with a novel, non-acetylatable VDR mutant (K413R) showed that the mutant VDR possesses enhanced responsiveness to 1,25D, in conjunction with reduced, but still significant, sensitivity to exogenous SIRT1, indicating that acetylation of lysine 413 is relevant, but that other acetylated residues in VDR contribute to modulation of its activity. We conclude that the acetylation of VDR comprises a negative feedback loop that attenuates 1,25D-VDR signaling. This regulatory loop is reversed by SIRT1-catalyzed deacetylation of VDR to amplify VDR signaling and 1,25D actions.

Background: Fiber-based prebiotic supplements are marketed for maintaining bowel health and promoting beneficial gut bacteria. However, the association between prebiotic supplement use and colorectal cancer risk and mortality is unknown. Methods: The association between prebiotic use and colorectal cancer risk and mortality was evaluated in postmenopausal women in the Women's Health Initiative study. Self-reported prebiotic use was documented at study enrollment. Adjudicated colorectal cancer cases and mortality were captured using medical and death records. Cox proportional hazards models were used to estimate the HR related to prebiotic use and colorectal cancer risk and mortality. Results: In total, 3,032 colorectal cancer cases were diagnosed during an average 15.4 years of follow-up. Overall, 3.7% of women used a prebiotic with psyllium, the major fiber type. Use of any prebiotic supplement was not associated with colorectal cancer risk or mortality. The type of prebiotic supplement (none vs. insoluble or soluble) was not associated with colorectal cancer risk; however, use of insoluble fiber prebiotics compared with none was associated with higher colorectal cancer mortality [HR, 2.79; 95% confidence interval (CI), 1.32–5.90; P = 0.007]. Likelihood ratio tests indicated no significant interactions between prebiotic use and other colorectal cancer risk factors, including metabolic syndrome. Conclusions: Prebiotic fiber supplement use was not associated with colorectal cancer risk. Insoluble, but not soluble, prebiotic fiber use was associated with higher colorectal cancer mortality. These findings do not support the promotion of prebiotic fiber supplements to reduce colorectal cancer risk or colorectal cancer mortality. Impact: Further investigation is warranted for findings regarding insoluble prebiotic fiber and higher colorectal cancer mortality in postmenopausal women.

Although hydrophobic bile acids have been demonstrated to exhibit cytotoxic and carcinogenic effects in the colorectum, ursodeoxycholic acid (UDCA) has been investigated as a potential chemopreventive agent. Vitamin D has been shown to play a role in both bile acid metabolism and in the development of colorectal neoplasia. Using a cross-sectional design, we sought to determine whether baseline circulating concentrations of the vitamin D metabolites 25(OH)D and 1,25(OH)2D were associated with baseline fecal bile acid concentrations in a trial of UDCA for the prevention of colorectal adenoma recurrence. We also prospectively evaluated whether vitamin D metabolite concentrations modified the effect of UDCA on adenoma recurrence. After adjustment for age, sex, BMI, physical activity, and calcium intake, adequate concentrations of 25(OH)D (≥30 ng/mL) were statistically significantly associated with reduced odds for high levels of total [OR, 0.61; 95% confidence interval (CI), 0.38–0.97], and primary (OR, 0.61; 95% CI, 0.38–0.96) bile acids, as well as individually with chenodeoxycholic acid (OR, 0.39; 95% CI, 0.24–0.63) and cholic acid (OR, 0.56; 95% CI, 0.36–0.90). No significant associations were observed for 1,25(OH)2D and high versus low fecal bile acid concentrations. In addition, neither 25(OH)D nor 1,25(OH)2D modified the effect of UDCA on colorectal adenoma recurrence. In conclusion, this is the first study to demonstrate an inverse relationship between circulating levels of 25(OH)D and primary fecal bile acid concentrations. These results support prior data demonstrating that vitamin D plays a key role in bile acid metabolism, and suggest a potential mechanism of action for 25(OH)D in colorectal cancer prevention. Cancer Prev Res; 9(7); 589–97. ©2016 AACR.