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Previous studies on cancer risk among agricultural producers have focused on occupational exposures, with only a few studies examining behavioral factors. The aim of this study was to understand cancer risky and preventative behaviors among the large farming population in Nebraska.A statewide cross-sectional study of farmers in Nebraska aged 19 and older was conducted in 2019 (n = 782). Multivariable logistic regression was used to examine factors associated with being up to date on cancer screening and with cancer risky and preventive behaviors.The 93.68% of the Nebraska farmers population do not meet the daily recommended consumption of fruits and vegetables, and 70.14% reported regular alcohol consumption. The proportion of adults up to date on cancer screening was 79.57% for breast, 67.55% for cervical, 85.54% for colorectal, and 46.05% for skin cancers. Compared to women, men had a higher odds of heavy alcohol consumption (aOR 2.96, 95% CI 1.94-4.56) and ever smoking 100 or more cigarettes (aOR 1.66, 95% CI 1.03-2.73). The odds of being current with skin cancer screening was higher among those with higher incomes (aOR 1.77, 95% CI 1.06-3.01). Compared to men aged 50-64, the odds of being current with prostate cancer screening was higher among men aged 65-74 (aOR: 2.65, 95% CI 1.10-7.31) and 75 and older (aOR: 7.73, 95% CI 2.03-51.73).Disparities in cancer screening and risk and preventive behaviors exist among farmers in Nebraska. The study highlights a need for continuing efforts to improve preventive cancer behaviors targeted to the farming population.

PURPOSE The purpose of this study was to examine differences between urban and rural primary care clinics in the use of colorectal cancer (CRC) screening methods and evidence-based interventions to promote CRC screening. METHODS This was a cross-sectional survey of primary care clinics in Nebraska. Surveys in paper form were sent out and followed up with telephone interviews to nonrespondents. Of the 375 facilities, 263 (70.1%) responded to the survey. FINDINGS Over 30% of urban clinics indicated that 80% or more of their patients were meeting the CRC guidelines compared to 18.3% of rural clinics (P = .03). Rural clinics were more likely than urban clinics to prefer the use of colonoscopy alone or in combination with stool tests (P = .02). The most common interventions for CRC screening included one-on-one patient education and use of computer-based pop-ups to remind providers. CONCLUSIONS In conclusion, we found some important differences between rural and urban primary care clinics in the implementation of CRC screening. Given that there is evidence for differences in preference for CRC screening methods (colonoscopy vs stool-based tests) between rural and urban community members, it is important to assess the effectiveness of different types of CRC screening interventions by comparing rural and urban primary care clinic patient populations.

Legends to Supplementary Figures S1-S4 from Chronic Bile Duct Injury Associated with Fibrotic Matrix Microenvironment Provokes Cholangiocarcinoma in p53-Deficient Mice

Supplementary Figures S1-S4 & Table S1 from Chronic Bile Duct Injury Associated with Fibrotic Matrix Microenvironment Provokes Cholangiocarcinoma in p53-Deficient Mice

Hepatocellular carcinoma is among the most common and lethal cancers in humans. Hepatocellular carcinoma is commonly associated with physical or functional inactivation of the p53 tumor suppressor, high levels of chromosomal instability, and disease conditions causing chronic cycles of hepatocyte death and regeneration. Mounting evidence has implicated regeneration-induced telomere erosion as a potential mechanism fueling genome instability. In mouse models of hepatocellular carcinoma, telomere dysfunction has been shown to enhance initiation of hepatic neoplasias yet constrain full malignant progression of these neoplasms possibly due to activation of a p53-dependent checkpoint and/or intolerable levels of genomic instability. Here, in a hepatocellular carcinoma–prone model brought about through toxin-induced hepatocyte injury and regeneration, we sought to determine the cooperative interactions of germ line p53 mutation and telomere dysfunction [produced by telomerase reverse transcriptase (mTERT) gene knockout]. In the setting of intact telomeres, p53 mutation had no effect on hepatocarcinogenesis, whereas in the setting of telomere dysfunction, p53 mutation enabled advanced hepatocellular carcinoma disease. Notably, there was no evidence of deletion or mutation of the wild-type p53 allele in the late generation mTert−/−p53+/− mice, suggesting that reduced levels of p53 potently enable hepatocellular carcinoma progression in the setting of telomere dysfunction. Thus, this study supports a model that, in the face of chronic liver damage, attenuated p53 function and telomere-induced chromosomal instability play critical and cooperative roles in the progression of hepatocellular carcinoma. (Cancer Res 2006; 66(9): 4766-73)

Supplementary Figure 2 from Cooperative Interactions of p53 Mutation, Telomere Dysfunction, and Chronic Liver Damage in Hepatocellular Carcinoma Progression

Supplementary Materials and Methods from Chronic Bile Duct Injury Associated with Fibrotic Matrix Microenvironment Provokes Cholangiocarcinoma in p53-Deficient Mice

Supplementary Figure 1 from Cooperative Interactions of p53 Mutation, Telomere Dysfunction, and Chronic Liver Damage in Hepatocellular Carcinoma Progression

Intrahepatic cholangiocarcinoma (CCA) is a lethal malignancy of the biliary epithelium associated with p53 mutations, bile duct injury, inflammation, and fibrosis. Here, to validate these processes in CCA, we developed a liver cirrhosis model driven by chronic intermittent toxin exposure, which provokes bile duct injury/necrosis and proliferation, fibroblast recruitment, and progressive extracellular matrix (ECM) changes. Fibrotic changes in the matrix microenvironment, typified by increased type I and III collagens and fibroblast recruitment, were shown to stimulate biliary epithelium hyperplasia with subsequent progression to malignant intrahepatic CCA only in mice harboring a p53 mutant allele. These murine CCAs bear histologic and genetic features of human intrahepatic CCA, including dense peritumoral fibrosis, increased inducible nitric oxide synthase, nitrotyrosine, and cyclooxygenase-2 expression, c-Met activation, cErbB2 overexpression, down-regulation of membrane-associated E-cadherin, and p53 codon 248 mutation. Thus, p53 deficiency, chronic bile duct injury/proliferation, and the fibrotic matrix microenvironment cooperate to induce intrahepatic CCA, highlighting the key role of the ECM microenvironment in this common liver cancer. (Cancer Res 2006; 66(13): 6622-7) (Cancer Res 2006; 66(13): 6622-7)

Compared to other races/ethnicities, the Latino population has a lower rate of adherence to colorectal cancer (CRC) screening guidelines. Previous studies have identified a variety of barriers to CRC screening in Latino populations but have not explored factors associated with barriers. The purpose of this study was to identify barriers to CRC screening and associated factors in a Midwest Latino population visiting an urban Federally Qualified Health Center (FQHC). We conducted a cross-sectional investigation of 68 Latinos at a FQHC from June to October 2017. We examined factors associated with scheduling, psychological, and financial barriers using t-test, ANOVA, and multiple linear regression analyses. Our participants reported low educational level, low income, and limited access to insurance or a primary care provider. Scheduling barriers are the highest barrier compared with psychological and financial barriers. Being married or coupled was the only predictor of higher scheduling barriers (P < .05). Being married or coupled was associated with higher psychological barriers in both univariate and multivariate analysis (P < .05). Higher education level was associated with higher psychological barriers in univariate (P < .05) but not multivariate analysis. Participants with lower vs. higher English proficiency had a higher financial barrier score in univariate (P < .05) but not multivariate analysis. Despite interventions targeting CRC screening barriers, including the provision of free at-home testing, perceived barriers persist. Bilingual patient navigators may help address needs for those with limited English proficiency to find and schedule free or reduced-fee colonoscopy services. People who are well educated are also at high risk of psychological barriers and should be targeted and given more education on the importance of CRC screening.

The overall incidence rate of cancer in Nebraska is higher than the national average with cancer being the second leading cause of death in the state. Interventions are required to reduce the cancer burden; however, further research is first needed to identify behavioral cancer risk factors and preventive behaviors among Nebraskans that can be targeted.A statewide cross-sectional survey of Nebraskans aged 19 and older was conducted in 2019 using an address-based sampling method (n = 1640). Multivariable logistic regression was used to examine factors associated with being up-to-date on cancer screening and with behavioral cancer risk factors and preventive behaviors.93.42% of Nebraskans did not meet the daily recommended consumption of fruits and vegetables, and 71.51% did not meet weekly physical activity guidelines. The proportion of adults up to date on cancer screening was 64.57% for breast, 68.83% for cervical, 69.01% for colorectal, and 24.07% for skin cancers. Individuals 65-74 (OR: 3.40, 95% CI: 1.52-7.62) and 75 or older (OR: 3.30, 95% CI: 1.35-8.07) were more likely to be current with their colorectal cancer screening compared to ages 50-64. Hispanics were less likely to be current with mammograms (OR: 0.06, 95% CI: 0.01-0.71) and ever screened for cervical cancer (OR:0.13, 95% CI: 0.02-0.94) compared to Non-Hispanic Whites.Disparities in cancer screening and risk and preventive behaviors exist in Nebraska.The study highlights a need for continuing efforts to improve preventive cancer behaviors for the entire population as well as some high-risk populations in Nebraska.

Background and Aim: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in Western countries. While obesity and diabetes are the hallmarks of NAFLD, it also develops in lean individuals in the absence of metabolic syndrome, with a prevalence of 7 percent in the U.S. and 25-30 percent in some Asian countries. NAFLD represents the spectrum of liver disease, starting with excess liver fat accumulation (NAFL) that can progress to nonalcoholic steatohepatitis (NASH), cirrhosis and ultimately hepatocellular carcinoma (HCC). To date, the pathogenesis of lean NASH-HCC is poorly understood and a mouse model is lacking. We aimed to develop a mouse model of lean NASH-HCC using a choline deficient and high trans-fat/sucrose/cholesterol diet to enable better understanding of its molecular pathogenesis. Methods: C57BL/6N mice were fed this diet starting at 4 weeks of age for 52 weeks and were compared to mice fed an isocaloric low fat control diet for the same duration. C57BL/6N mice were chosen instead of the C57BL/6J mice due to the high susceptibility of C57BL/6J mice to diet-induced obesity. The plasma and tumor fatty acid profile of these mice was also investigated. Results: Nearly 61% of the mice developed lean NASH-HCC. These mice showed reduction of plasma polyunsaturated fatty acids (PUFAs) (linolenic acids (α and γ, ω-3 and ω-6, respectively), eicosapentanoic acid (ω-3), docosahexanoic acid (ω-3), and linoleic acid (ω-6)) and increasing levels over time in mice with pre-malignant lesions. Conclusions: We developed a novel high penetrance diet-induced lean NASH-HCC mouse model. Plasma PUFA levels were reduced with tumor progression in parallel with reduced expression of genes controlling desaturase expression suggesting their potential use as biomarkers for lean NASH-HCC progression as well as chemopreventive molecules.

Transitions between e-cigarettes and cigarettes are common among tobacco users, but empirical evidence on the health outcomes of switching tobacco products is scarce.To examine changes in urinary biomarkers between baseline and 1-year follow-up among adult tobacco users switching between e-cigarettes and cigarettes.This cohort study used data from wave 1 (baseline, September 2013 to December 2014) and wave 2 (1-year follow-up, October 2014 to October 2015) of the Population Assessment of Tobacco and Health Study. A subset of the probability sample of US adults who voluntarily provided biospecimens at 2 waves was analyzed. Participants were divided into 3 mutually exclusive groups at baseline: exclusive cigarette smokers, exclusive e-cigarette users, and dual users. Data analysis was performed in 2021.Harmful and potentially harmful constituents included nicotine metabolites, tobacco-specific nitrosamines (TSNAs; including 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol [NNAL]), metals, polycyclic aromatic hydrocarbons (PAHs), and volatile organic compounds (VOCs).Within-participant changes in 55 urinary biomarkers of exposure (BOEs) to harmful and potentially harmful constituents were examined using multivariable regression models.Among 3211 participants (55.6% women, 68.3% White, 13.2% Black, and 11.8% Hispanic) at baseline, 21.9% of exclusive cigarette users, 42.8% of exclusive e-cigarette users, and 62.1% of dual users changed product use at follow-up (all percentages are weighted). There was a significant reduction in urine concentrations of TSNAs, PAHs, and VOCs when users transitioned from exclusive cigarette to exclusive e-cigarette use, with a 92% decrease in NNAL, from a mean of 168.4 pg/mg creatinine (95% CI, 102.3-277.1 pg/mg creatinine) to 12.9 pg/mg creatinine (95% CI, 6.4-25.7 pg/mg creatinine; P .001). A similar panel of BOEs decreased when dual users transitioned to exclusive e-cigarette use; NNAL levels decreased by 96%, from a mean of 143.4 pg/mg creatinine (95% CI, 86.7-237.0 pg/mg creatinine) to 6.3 pg/mg creatinine (95% CI, 3.5-11.4 pg/mg creatinine; P .001). Nicotine metabolites, TSNAs, PAHs, and VOCs significantly increased when baseline exclusive e-cigarette users transitioned to exclusive cigarette use or dual use. Switching from exclusive cigarette use to dual use was not associated with significant decreases in BOEs.This national cohort study provides evidence on the potential harm reduction associated with transitioning from exclusive cigarette use or dual use to exclusive e-cigarette use. e-Cigarettes tend to supplement cigarettes through dual use instead of cessation at the population level. Continuous monitoring of BOE at the population level and assessment of BOE change by product transition are warranted, as well as defined adverse health outcomes.

Background Cancer clinical trials (CCTs) are essential for cancer care, yet the evidence is scarce when it comes to racial disparities in CCT participation among cancer survivors in the Midwest. This study aimed to 1) assess disparities in the awareness of and willingness to participate in CCTs between African American and White cancer survivors; and 2) compare perceptions about CCTs between the two racial groups. Methods The study was based on cross-sectional data from the survey “Minority Patient Participation in Cancer Clinical Trials” that collected information from 147 Black and White cancer survivors from Nebraska between 2015 and 2016. Chi-square tests and logistic regressions were used to assess differences between Black and White cancer survivors regarding their awareness, willingness, and perceptions associated with CCT participation. Results After adjusting for the effects of socio-demographic, health status, and psychosocial variables, Black cancer survivors were much less likely than White cancer survivors to be aware of CCTs (AOR 0.26; CI 0.08–0.81), to express willingness to participate in CCTs (AOR 0.03; CI 0.01, 0.32) and to actually participate in CCTs (AOR 0.13; CI 0.04–0.38). Black cancer survivors reported a lower level of trust in physicians and were less likely than White cancer survivors to believe that CCTs make a significant contribution to science. Conclusions Relative to White cancer survivors, Black cancer survivors had much lower awareness of and willingness to participate in CCTs. Part of these differences might be related to the differential perception of CCTs, psychosocial factors, and trust in physicians between the two groups.

Background Non-alcoholic fatty liver disease (NAFLD) ranks first among liver diseases in Western countries. NAFLD is typically associated with obesity and diabetes, however it also develops in lean individuals without metabolic syndrome. The prevalence of lean NAFLD is 7 percent in the U.S. and 25–30 percent in some Asian countries. NAFLD starts with excess liver fat accumulation (NAFL), progresses to nonalcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma (HCC). The pathogenesis of lean NASH-HCC and how it differs from obese NASH-HCC is not well understood. Methods In this work, we generated a mouse model of lean and obese NASH-HCC using a choline deficient/high trans-fat/fructose/cholesterol diet and a choline supplemented/high trans-fat/fructose/cholesterol diet, respectively, to compare progression to NASH-HCC in lean versus obese mice. Comparisons were made at the organismal, histological, and molecular level by investigating fatty acid metabolism in the plasma of these mice. Results Obese mice showed more pronounced glucose intolerance and insulin resistance, higher levels of plasma cholesterol and triglycerides, and higher penetrance of NASH compared to lean mice. Despite the abnormal metabolic profile of obese mice, male obese and lean mice developed HCC with similar penetrance (53.3% and 53.8%, respectively), albeit lean mice showed faster tumor progression as evidenced by the larger tumor size and lower HCC-free survival. None of the female lean mice developed HCC, while 50% of female obese mice developed HCC. Both groups of mice showed a reduction in plasma polyunsaturated fatty acids (PUFAs), however, the levels were higher towards the endpoint in obese mice compared to lean mice. Conclusions Unhealthy diet composition appears to drive progression to NASH-HCC rather than the organismal effects of obesity. PUFA levels may increase due to systemic inflammation in obese mice and act as suppressors of tumor progression, thus delaying HCC progression in obese mice compared to lean mice. These models could be used to further dissect the molecular pathogenesis of lean and obese NASH-HCC and address the mechanisms whereby PUFAs may be implicated in hepatocarcinogenesis.

Compared to other races/ethnicities, the Latino population has a lower rate of adherence to colorectal cancer (CRC) screening guidelines. Previous studies have identified a variety of barriers to CRC screening in Latino populations but have not explored factors associated with barriers. The purpose of this study was to identify barriers to CRC screening and associated factors in a Midwest Latino population visiting an urban Federally Qualified Health Center (FQHC). We conducted a cross-sectional investigation of 68 Latinos at a FQHC from June to October 2017. We examined factors associated with scheduling, psychological, and financial barriers using t-test, ANOVA, and multiple linear regression analyses. Our participants reported low educational level, low income, and limited access to insurance or a primary care provider. Scheduling barriers are the highest barrier compared with psychological and financial barriers. Being married or coupled was the only predictor of higher scheduling barriers (P.05). Being married or coupled was associated with higher psychological barriers in both univariate and multivariate analysis (P.05). Higher education level was associated with higher psychological barriers in univariate (P.05) but not multivariate analysis. Participants with lower vs. higher English proficiency had a higher financial barrier score in univariate (P.05) but not multivariate analysis. Despite interventions targeting CRC screening barriers, including the provision of free at-home testing, perceived barriers persist. Bilingual patient navigators may help address needs for those with limited English proficiency to find and schedule free or reduced-fee colonoscopy services. People who are well educated are also at high risk of psychological barriers and should be targeted and given more education on the importance of CRC screening.

Background Previous studies have explored surgery refusal among female breast cancer patients. However, little attention has been given to other therapies in both females and males. The goal of this study was to determine the potential role of gender on recommended hormone therapy, chemotherapy, radiation therapy, and surgery refusal and to describe other determinants of refusal. Materials and Methods A retrospective study of the National Cancer Database (NCDB) between 2004 and 2016 was conducted. The outcome was whether patients accepted or refused the recommended treatment. We examined four different outcome variables (hormone therapy, chemotherapy, radiation therapy, and surgery) relation to gender and other factors. Results A total of 906,342 breast cancer patients met the eligibility criteria for hormone therapy, 1,228,132 for surgery, 596,229 for chemotherapy, and 858,050 for radiation therapy. The odds of refusing hormone therapy and surgery in males were 17% (AOR=0.83; 95% CI: 0.75-0.92) and 33% (AOR=0.67; 95% CI: 0.50-0.90) lower compared to female patients, respectively. The odds of refusing radiation therapy were 14% higher in males compared to females (AOR=1.14; 95% CI:1.03-1.30). Older age and lack of insurance were significantly associated with each treatment refusal. Conclusion Female patients tend to refuse hormone therapy and surgery compared to males. A marginally statistically significant gender differences was found for radiotherapy refusal. The providers and other stakeholders can utilize the current findings to identify the risk groups and barriers associated with refusal for each treatment and to develop interventions. MicroAbstract We used largest data to determine the potential role of gender and other factors on breast cancer treatment refusal in the US. Females tend to refuse hormone therapy and surgery compared to males. Demographic and clinical factors association with treatment varied by treatment type. The results can be used to increase the treatment acceptance rate.

Background: The gut microbiome plays a critical role in modulating the therapeutic effect of immune checkpoint inhibitors (ICIs). Proton pump inhibitors (PPIs) are commonly used in cancer patients and may affect the gut microbiome by altering gut pH. Objective: To evaluate if concurrent use of PPI is associated with overall survival (OS) and progression-free survival (PFS) in patients with stage IV non–small-cell lung cancer (NSCLC), melanoma, renal cell carcinoma, transitional cell carcinoma, or head and neck squamous cell carcinoma. Methods: This was a single-center retrospective cohort study of advanced cancer adult patients who received nivolumab or pembrolizumab between September 1, 2014, and August 31, 2019. Concomitant PPI exposure was defined as PPI use 0 to 30 days before or after initiation of ICIs. Treatment outcome was OS and PFS. Results: A total of 233 patients were included in our study. Concomitant PPI use was not significantly associated with OS (hazard ratio [HR] = 1.22; 95% CI = 0.80-1.86) or PFS (HR = 1.05; 95% CI = 0.76-1.45) in patients with ICI use. The effect estimates were robust after adjusting for covariates in multivariate analysis and in patients with NSCLC. Conclusion and Relevance: Concomitant PPI use was not associated with the effectiveness of nivolumab or pembrolizumab. Certain predictors of survival outcomes related to PPI use in patients receiving immunotherapy, such as the time window and indication of PPI exposure and autoimmune disorders, should be explored in the future to better carve out the impact of PPI on the effectiveness of ICI use.

To examine the association of muscle-strengthening activities (MSA) and cancer mortality. We pooled data from the 1998 to 2009 National Health Interview Survey (NHIS), which were linked to records in the National Death Index. Mortality follow-up was through 31 December 2011. Based on U.S. federal guidelines for physical activity, we dichotomized MSA and compared those who performed MSA twice a week or more to others with lower MSA. We also examined dose–response relationship of MSA frequency with cancer mortality. Hazard ratios (HR) from Cox regression were computed to estimate the association of MSA with the risk of cancer mortality. Mean follow-up was 7.9 years and the analysis sample size was 310,282. Covariate-adjusted results showed that meeting the MSA guideline was associated with a 19% lower risk of cancer mortality (HR 0.81, 95% CI 0.73, 0.90). We found no evidence of a dose–response relationship between the frequency of performing MSA and cancer mortality. Adhering to the U.S. federal guideline for MSA is associated with lower cancer mortality. Public health programs and policy for cancer prevention and control should promote MSA to further reduce cancer mortality.

Background The incidence of liver cancer has more than tripled since 1980. Hepatectomy represents the major curative treatment for liver cancer. The risk factors associated with 90-day mortality after hepatectomy are not well understood and there are currently no good prediction models for this outcome. The objectives of the current study were to identify risk factors of 90-day mortality after hepatectomy in patients with hepatocellular carcinoma and to develop an integer-based risk score using the National Cancer Database. Methods Hepatectomies recorded in the National Cancer Database during 2004-2012 were reviewed for 90-day mortality. Risk factors were identified by multivariate logistic regression models. An integer-based risk score was developed using the β coefficients derived from the logistic regression model and tested for discriminatory ability. According to the total risk score, patients were grouped into 4 risk groups. Results The overall 90-day mortality was 10.2%. Ten risk factors were identified, which included sex, age, race/ethnicity, insurance status, education, annual hospital volume, stage, tumor grade, Charlson-Deyo Score, and surgical procedure. The risk of 90-day mortality was stratified into 4 groups. The calculated 90-day mortality rates were 2.47%, 5.88%, 12.58%, and 24.67% for low-risk, medium-risk, high-risk, and excessive-risk groups, respectively. An area under the receiver operating characteristic curve of 0.69 was obtained for model discrimination. Conclusions The integer-based risk score we developed could easily quantify each patient's risk level and predict 90-day mortality after hepatectomy. The stratified risk score could be a useful addition to perioperative risk management and a tool to improve 90-day mortality after hepatectomy.

Colorectal cancer (CRC) screening rates remain low in Latino communities. We sought to determine the screening awareness and attitudes in Omaha, Nebraska.We interviewed 150 Latinos at an urban Federally Qualified Health Center, June-October 2017. Chi-square or Fisher-exact tests and multiple logistic regression models were used for data analysis.Participants reported low educational attainment, low income, and limited access to insurance or a primary provider. Less than one-third of participants aged 50 + had ever heard of FOBT (32.6%) or colonoscopy (30.4%). For individuals 50+, access to a primary care provider (p = .03) and knowing the screening initiation age (p = .03) were associated with ever having a colonoscopy. Higher knowledge score was a strong predictor of any CRC screening.Knowledge predicted screening, suggesting interventions should aim to educate this population regarding CRC screening guidelines and options and work with stakeholders to make CRC screening more accessible.

Background Association between high adiposity and the clinical progression of dementia remains puzzling. Objective To separately examine the association between body mass index (BMI) and cognitive, functional, and behavioral declines before, at, and after diagnosis of dementia, and further stratified by age groups, and sex. Methods A total of 1,141 individuals with incident dementia were identified from the Uniform Data Set of the National Alzheimer's Coordinating Center. Cognitive function was evaluated by Mini-Mental State Exam, functional abilities were assessed using Functional Activities Questionnaire, and behavioral symptoms were captured by Neuropsychiatric Inventory Questionnaire at each follow-up visit. We used separate linear-mixed effects models to examine the association. Results Compared to moderate baseline BMI, high baseline BMI was associated with 0.30-point slower annual progression rates in functional decline. For individuals aged 76 and over, high baseline BMI was associated with 0.42-point faster progression rates in cognitive decline annually. A U-shaped association between baseline BMI and cognitive decline was observed among men. Conclusion BMI levels before dementia diagnosis may facilitate the identification of different risk profiles for progression rates of cognitive and functional declines in individuals who developed dementia.

Objective High rates of maternal mortality persist in Low and Middle Income countries, despite increasing rates of facility-based births, suggesting a need to focus on quality of maternity care. The purpose of the current study was to evaluate provider perspectives on the implementation of material taught during an evidence-based medical education session aimed at reducing common causes of maternal death in government hospitals in India. Design Several months after the training, labor room nurses and physicians from twenty-two hospitals participated in semi-structured focus group discussions. Setting Training sessions were held in an off-site location in each of fourteen districts across Kerala, India. Participants Nurses and physicians working in labor and delivery wards within government hospitals. Intervention Participants were trained on evidence-based practices to treat and prevent common causes of maternal death. Training was a combination of lecture and hands-on practice, conducted over a single working day in a classroom setting. Measurements and findings Main items of discussion were challenges to implementing material taught in the training session and identification of successful strategies to adopt the recommended standards of care. Primary barriers to implementation of quality standards were provider unwillingness to apply new techniques, inadequate infrastructure, challenges with staffing capacity and lack of required materials and equipment. Facilitators to implementing standards of care included staff motivation, supportive leadership and co-training of nurses and doctors. Key conclusions In international settings, clinical uptake of evidence-based material taught in a classroom format may differ by physician attitude and may be moderated by external factors such as infrastructure quality and equipment availability. In some circumstances, highly motivated staff may overcome external barriers through effort and persistence. Implications for practice Continuing medical education aimed to improve utilization of evidence-based maternity care in low- and middle-income countries may have limited effect without complementary support from hospital administration and provision of adequate infrastructure, equipment and materials to support evidence-based practice.

Prostate cancer (PCa) is the most commonly diagnosed cancer among Nigerian men. The prevalence of PCa varies within Nigeria, with the highest prevalence of 1046 per 100,000 in men over the age of 40 reported in Lagos. Unfortunately, 40% of these men are diagnosed with locally advanced disease and 35% with metastatic disease. Given the ability to screen for PCa among high-risk individuals, late stage diagnosis of PCa could be potentially reduced through education of men so that they seek screening. Along these lines, it is important to assess a population's knowledge and awareness on PCa and screening. Our study addresses this issue by evaluating awareness and attitudes of Nigerian men in Abuja on PCa and screening. Our results revealed gaps in awareness and perception of susceptibility to PCa and low levels of PCa screening. Factors such as age, education level, and income affected PCa awareness. In conclusion, our study points to the need to educate younger men of lower education and socioeconomic status in Nigeria with the aim to increase screening and earlier detection of PCa.

Cervical cancer is preventable; however, despite the existence of primary and secondary means of prevention, its incidence is still higher in certain socioeconomic groups and countries, suggesting gaps in cervical cancer prevention. The objective of this study was to evaluate the knowledge and awareness of health sciences university students in Cyprus regarding HPV and cervical cancer in order to better guide the future development of educational programs to improve cervical cancer prevention. This was a cross-sectional study of 178 university health sciences students in Cyprus using a validated questionnaire on HPV and cervical cancer prevention. Analysis of the completed questionnaires revealed moderate levels of knowledge and awareness with an overall mean score of 23.32 out of 33 on HPV and 8.12 out of 13 on cervical cancer, a score of 9.25 out of 14 on HPV vaccines, and a score of 5.93 out of 9 on cervical cancer screening. Older students achieved higher scores compared to younger students (mean score of 6.76 for 18–22 years old, 9.44 for 23–28 years old, and 10.25 for 29–38 years old; p

The incidence rate of cervical cancer varies by geographic region, with less developed regions showing the highest rates. All risk factors for cervical cancer are actually preventable if appropriate lifestyle changes are adopted. In addition, vaccines protecting against the majority of human papilloma virus (HPV) high-risk types have been developed. Even though cervical cancer is preventable, not all women are aware of this or how it can be prevented. Thus, it is essential for every nation to assess the level of knowledge among women of cervical cancer and HPV prevention. In this work, we assessed the level of awareness and attitudes of Greek female healthcare workers on cervical cancer and HPV prevention through the delivery of a validated questionnaire between March and June 2012 in three hospitals in Greece. Our results show that there exist gaps in the knowledge of women on this topic, especially in terms of the newest information on cervical cancer prevention through HPV testing and vaccination. In fact, only 80% of surveyed women knew about the existence of HPV testing. We propose that more information needs to be transmitted to Greek women and men on HPV testing and vaccination. Even though the incidence of cervical cancer is not extremely high in Greece, this number can easily change, especially in the face of the economic crisis and the increasing rates of migration, which can result in higher rates of HPV infection in the population if no measures for HPV prevention are implemented.

Introduction Colorectal cancer (CRC) screening rates are lower in rural areas in the USA. To guide the design of interventions to improve CRC screening, a systematic review was conducted to identify CRC screening barriers for rural populations. Methods A search was conducted in four literature databases - Medline, CINAHL, Embase, and Scopus - for articles from 1998 to 2017 that examine CRC screening barriers in rural areas. This review included a total of 27 articles reporting perceived CRC screening barriers by rural residents or providers or examining factors associated with CRC screening of rural populations in the USA. Results The most frequently reported barriers were high screening cost and lack of insurance coverage, embarrassment or discomfort undergoing screening, lack of knowledge or perceived need on CRC screening, and lack of physician recommendation. These barriers were confirmed in quantitative studies examining their association with CRC screening status. Age, marital status, and race/ethnicity were the most frequently reported factors associated with CRC screening in rural areas. Lack of prevention attitude toward cancer, perceived lack of privacy, shortage of specialists, and distance to test facilities were reported as rural-specific barriers for CRC screening. Conclusions Main barriers for CRC screening at both the individual and healthcare system level are identified in rural areas and they are in line with those found in urban areas in general. In particular, lack of prevention attitude toward cancer, perceived lack of privacy, shortage of specialists, and distance to test facilities disproportionately hamper CRC screening for rural Americans.

Objectives: Moderate-to-vigorous physical activity provides multiple benefits to women after childbirth. To achieve these benefits, the recommendation that adults obtain, 150 min of moderate-to-vigorous physical activity per week and reduce sedentary behaviors, also applies to women in the post-partum phase of the life span. However, research examining the moderate-to-vigorous physical activity and sedentary behaviors of women with young children (0–2 years) is limited. A greater understanding of these behaviors from a nationally representative sample is needed. Therefore, the primary objective of this study was to determine the levels of moderate-to-vigorous physical activity and sedentary behaviors of a nationally representative sample of women with young children within the United States. A secondary objective was to examine the influence of body mass index and sociodemographic factors on these behaviors. Methods: Cross-sectional data from four cycles of the National Health and Nutrition Examination Survey (2007–2008, 2009–2010, 2011–2012, and 2013–2014) were used for analysis. Descriptive statistics were calculated and a generalized linear model was used to investigate associations between mean minutes of moderate-to-vigorous physical activity, sedentary activity, body mass index, and sociodemographic variables. Discussion: Women with young children (n = 477) obtained 634 min in moderate-to-vigorous physical activity per week and this was positively associated with having a higher income (p

OBJECTIVE To identify patient, provider, and delivery system-level factors associated with colorectal cancer (CRC) screening and validate findings across multiple data sets. DESIGN A concurrent mixed-methods design using electronic health records, provider survey, and provider interview. SETTING Eight primary care accountable care organization clinics in Nebraska. MEASURES Patients' demographic/social characteristics, health utilization behaviors, and perceptions toward CRC screening; provider demographics and practice patterns; and clinics' delivery systems (eg, reminder system). ANALYSIS Quantitative (frequencies, logistic regression, and t tests) and qualitative analyses (thematic coding). RESULTS At the patient level, being 65 years of age and older (odds ratio [OR] = 1.34, P < .001), being non-Hispanic white (OR = 1.93, P < .001), having insurance (OR = 1.90, P = .01), having an annual physical examination (OR = 2.36, P < .001), and having chronic conditions (OR = 1.65 for 1-2 conditions, P < .001) were associated positively with screening, compared with their counterparts. The top 5 patient-level barriers included discomfort/pain of the procedure (60.3%), finance/cost (57.4%), other priority health issues (39.7%), lack of awareness (36.8%), and health literacy (26.5%). At the provider level, being female (OR = 1.88, P < .001), having medical doctor credentials (OR = 3.05, P < .001), and having a daily patient load less than 15 (OR = 1.50, P = .01) were positively related to CRC screening. None of the delivery system factors were significant except the reminder system. Interview data provided in-depth information on how these factors help or hinder CRC screening. Discrepancies in findings were observed in chronic condition, colonoscopy performed by primary doctors, and the clinic-level system factors. CONCLUSIONS This study informs practitioners and policy makers on the effective multilevel strategies to promote CRC screening in primary care accountable care organization or equivalent settings. Some inconsistent findings between data sources require additional prospective cohort studies to validate those identified factors in question. The strategies may include (1) developing programs targeting relatively younger age groups or racial/ethnic minorities, (2) adapting multilevel/multicomponent interventions to address low demands and access of local population, (3) promoting annual physical examination as a cost-effective strategy, and (4) supporting organizational capacity and infrastructure (eg, IT system) to facilitate implementation of evidence-based interventions.

Objectives To examine (1) the association between household socioeconomic status (SES) and whether a household spends money on cigarettes and (2) socioeconomic variations in proportion of total household expenditure spent on cigarettes among smoking households. Methods We pooled data from six consecutive years, 2010–2015, of the Consumer Expenditure Interview Survey. The interviews involved a structured questionnaire about household income, demographics and expenditures including expenditure on cigarettes. Households that reported cigarette expenditure in the previous 3 months were distinguished as smoking households. SES indicators were household poverty status, education and occupation of the head of household. Logistic regression was used to assess the association of household smoking status with SES. Fractional logistic regression was used to assess the association of cigarette expenditure as a proportion of total household expenditure with SES. The analysis sample size was 39 218. Results The probability of spending money on cigarettes was higher among lower SES households. Households in poverty compared with those above 300% of poverty threshold had 1.86 (95% CI 1.61 to 2.16), households headed by a person with less than high school education compared with those headed by a person with at least a bachelor’s degree had 3.37 (95% CI 2.92 to 3.89) and households headed by a blue-collar work compared with those headed by a person in a managerial occupation had 1.45 (95% CI 1.26 to 1.66) higher odds of spending money on cigarettes. Similarly, the proportion of total household expenditure spent on cigarettes was higher among lower SES smoking households. Conclusion Lower SES households are more likely to spend money on cigarettes and spend a larger proportion of their total expenditure on cigarettes. We recommend strategies effective in reducing smoking among low SES smokers.

Hepatocellular carcinoma (HCC) is one of the fastest growing causes of cancer-related death in the USA. Studies that investigated the impact of HCC therapeutic delays are limited to single centers, and no large-scale database research has been conducted. This study investigated the association of surgical delay and survival in HCC patients. Patients underwent local tumor destruction and hepatic resection for stages I–III HCC were identified from the 2004 to 2013 Commission on Cancer’s National Cancer Database. Surgical delay was defined as > 60 days from the date of diagnosis to surgery. Generalized linear-mixed model assessed the demographic and clinical factors associated with delay, and frailty Cox proportional hazard analysis examined the prognostic factors for overall survival. A total of 12,102 HCC patients met the eligibility criteria. Median wait time to surgery was 50 days (interquartile range, 29–86), and 4987 patients (41.2%) had surgical delay. Delayed patients demonstrated better 5-year survival for local tumor destruction (29.1 vs. 27.6%; P = .001) and resection (44.1 vs. 41.0%; P = .007). Risk-adjusted model indicated that delayed patients had a 7% decreased risk of death (HR, 0.93; 95% CI, 0.87–0.99; P = .027). Similar findings were also observed using other wait time cutoffs at 50, 70, 80, 90, and 100 days. A plausible explanation of this finding may be case prioritization, in which patients with more severe and advanced disease who were at higher risk of death received earlier surgery, while patients with less-aggressive tumors were operated on later and received more comprehensive preoperative evaluation.

Background Data from the Surveillance, Epidemiology, and End Results (SEER) revealed that the incidence of pediatric cancer in Nebraska exceeded the national average during 2009–2013. Further investigation could help understand these patterns. Methods This retrospective cohort study investigated pediatric cancer (0–19 years old) age adjusted incidence rates (AAR) in Nebraska using the Nebraska Cancer Registry. SEER AARs were also calculated as a proxy for pediatric cancer incidence in the United States (1990–2013) and compared to the Nebraska data. Geographic Information System (GIS) mapping was also used to display the spatial distribution of cancer in Nebraska at the county level. Finally, location–allocation analysis (LAA) was performed to identify a site for the placement of a medical center to best accommodate rural pediatric cancer cases. Results The AAR of pediatric cancers was 173.3 per 1,000,000 in Nebraska compared to 167.1 per 1,000,000 in SEER. The AAR for lymphoma was significantly higher in Nebraska (28.1 vs. 24.6 per 1,000,000; p = 0.009). For the 15–19 age group, the AAR for the 3 most common pediatric cancers were higher in Nebraska (p 2 h driving distance to care facilities showed at least a 10% higher incidence than the overall state AAR. GIS mapping identified a second potential treatment site that would alleviate this geographic burden. Conclusions Regional differences within Nebraska present a challenge for rural populations. Novel use of GIS mapping to highlight regional differences and identify solutions for access to care issues could be used by similar states.

Background Hepatocellular carcinoma (HCC) is among the leading causes of cancer deaths in China. Considering its poor prognosis when diagnosed late, Chinese guidelines recommend biannual screening for HCC with abdominal ultrasound and serum α-fetoprotein (AFP) test for high-risk populations. Objectives To investigate the practice, knowledge, and self-perceived barriers for HCC screening among high-risk hospital patients in China. Methods An interview-based questionnaire was conducted among Chinese patients with chronic hepatitis B and/or chronic hepatitis C infection from outpatient clinics at 2 tertiary medical institutions in Shanghai and Wuhan, China. Findings Among 352 participating patients, 50.0% had routine screening, 23.3% had irregular screening, and 26.7% had incomplete or no screening. Significant determinants for screening included higher level of education, underlying liver cirrhosis, a family history of HCC, and better knowledge concerning viral hepatitis, HCC, and HCC screening guidelines. Moreover, factors associated with better knowledge were younger age, female gender, urban residency, education level of college or above, annual household income of greater than 150,000 RMB, and longer duration of hepatitis infection. The 3 most common barriers reported for not receiving screening were not aware that screening for HCC exists (41.5%), no symptoms or discomfort (38.3%), and lack of recommendation from physicians (31.9%). Conlusions Health care professionals and community leaders should actively inform patients regarding the benefits of HCC screening through design of educational programs. Such interventions are expected to increase knowledge about HCC and HCC screening, as well as improve screening adherence and earlier diagnosis.

While most ecological studies have shown that higher levels of point-of-sale (POS) cigarette marketing are associated with larger proportions of residents from lower socioeconomic and minority backgrounds in neighborhoods, there are no studies that examine individual-level social disparities in exposure to POS cigarette marketing among smokers in the United States. Our aim was to examine these disparities in a Midwestern metropolitan area in the United States. We conducted a telephone survey to collect data on 999 smokers. Cigarette marketing was measured by asking respondents three questions about noticing advertisements, promotions, and displays of cigarettes within their respective neighborhoods. The questions were combined to create a summated scale. We estimated ordered logistic regression models to examine the association of sociodemographic variables with exposure to POS cigarette marketing. Adjusted results showed that having a lower income (p < 0.003) and belonging to a race/ethnicity other than “non-Hispanic White” (p = 0.011) were associated with higher levels of exposure to POS cigarette marketing. The results highlight social disparities in exposure to POS cigarette marketing in the United States, which can potentially be eliminated by banning all forms of cigarette marketing.

Background Causal relationships have been previously established between smoking and various cancers. In Cyprus, 39 % of men and 14 % of women reported daily smoking in 2008. The objective of this study was to compare the incidence of tobacco-related cancers to all other cancers by district and rural–urban classification to understand the impact of tobacco in Cyprus. Methods Data on lung, urinary bladder, oral, pharyngeal, head/neck, and laryngeal cancers were obtained from the Cyprus Cancer Registry (1998–2008). There were 3,635 patients with tobacco-related cancers and 18,780 with non-tobacco cancers. Univariate analysis comparing tobacco-related cancers and all other cancers were conducted with regards to age at diagnosis, age groups, sex, smoking status, disease stage, and rural/urban status, with a p-value of 0.05 considered significant. Smoking prevalence, lung cancer, and bladder cancer rates of Cyprus were also compared to a number of other European countries. Results Patients with tobacco-related cancers were older than those with non-tobacco cancers (mean age 67.2 ± 12.4 vs. 62.4 ± 17.1, p

Cyprus maintains a population-based cancer registry that allows for in-depth study of cancer in a culturally- and environmentally-unique setting. Using eleven years of collected data (1998-2008), we present the first comprehensive analysis of cancer in Cyprus. We calculated gender-specific, world age-adjusted incidence rates and time trends for the 26 most incident cancers. This study revealed that overall world age-standardized rates among males increased from 195.4 cases per 100,000 in 1998-2002 to 239.0 cases per 100,000 in 2006-2008. For the entire eleven-year period, prostate, lung, colorectal, and bladder cancers were the most incident cancers among males. Among females, the overall world age-standardized rate increased from 180.6 cases per 100,000 in 1998-2002 to 217.1 cases per 100,000 in 2006-2008. Over the entire period, breast, colorectal, uterine, and thyroid were the most incident cancers in females. There were sixteen sex-specific cancers that indicated statistically significant increasing incidence trends over the study period, and no types for which the rate was significantly decreasing. Thyroid cancer illustrated rapid increases in rates. Results were compared to other Mediterranean European registries reported in Cancer Incidence in 5 Continents report for 1997-2002. Overall cancer incidence in Cyprus is lower than that of Southern Mediterranean countries, and given the known environmental risk factors in Cyprus, the low rate of lung cancer is especially interesting. The epidemiologic patterns reported in this study open the door for future etiologic studies to elucidate role of environmental and lifestyle factors of cancer in this population and highlight opportunities for cancer prevention and control.

Hepatocellular carcinoma is among the most lethal and prevalent cancers in the human population. Despite its significance, there is only an elemental understanding of the molecular, cellular and environmental mechanisms that drive disease pathogenesis, and there are only limited therapeutic options, many with negligible clinical benefit. This Review summarizes the current state of knowledge of this, the most common and dreaded liver neoplasm, and highlights the principal challenges and scientific opportunities that are relevant to controlling this accelerating global health crisis.

Although nonhomologous end-joining (NHEJ) deficiency has been shown to accelerate lymphoma formation in mice, its role in suppressing tumors in cells that do not undergo V(D)J recombination is unclear. Utilizing a tumor-prone mouse strain ( ink4a / arf −/− ), we examined the impact of haploinsufficiency of a NHEJ component, DNA ligase IV (Lig4), on murine tumorigenesis. We demonstrate that lig4 heterozygosity promotes the development of soft-tissue sarcomas that possess clonal amplifications, deletions, and translocations. That these genomic alterations are relevant in tumorigenesis is supported by the finding of frequent mdm2 amplification, a known oncogene in human sarcoma. Together, these findings support the view that loss of a single lig4 allele results in NHEJ activity being sufficiently reduced to engender chromosomal aberrations that drive non-lymphoid tumorigenesis.