Racial and Ethnic Disparities in Serious Illness Conversation Quality during the COVID-19 Pandemic.

CONTEXT: The COVID-19 pandemic disproportionately impacted non-Hispanic Black and Hispanic patients. However, little is known about the quality of serious illness communication in these communities during this time. OBJECTIVE: We aimed to determine whether racial and ethnic disparities manifested in serious illness conversations during the pandemic. METHODS: This was a retrospective, observational, cohort study of adult patients with a documented serious illness conversation from March 2020 to April 2021. Serious illness conversation documentation quality was assessed by counting the median number (IQR) of conversation domains and their elements included in the documentation. Domains included (1) values and goals, (2) prognosis and illness understanding, (3) end-of-life care planning, and (4) life-sustaining treatment preferences. A multivariable ordinal logistic regression analysis was conducted to assess associations between differences in serious illness documentation quality with patient race and ethnicity. RESULTS: Among 291 patients, 149 (51.2%) were non-Hispanic White; 81 (27.8%) were non-Hispanic Black; and 61 (21.0%) were Hispanic patients. Non-Hispanic Black patients were associated with fewer domains (OR 0.46 [95% CI 0.25, 0.84]; P=.01) included in their serious illness conversation documentation compared to non-Hispanic White patients. Both non-Hispanic Black (OR 0.35 [95% CI 0.20, 0.62]; P<.001) and Hispanic patients (OR 0.29 [95% CI 0.14, 0.58]; P<.001) were associated with fewer elements in the values and goals domain compared to non-Hispanic White patients in their serious illness documentation. CONCLUSION: During the COVID-19 pandemic, serious illness conversation documentation among non-Hispanic Black and Hispanic patients was less comprehensive compared to non-Hispanic White patients.

Detecting Variation in Clinical Practice Patterns for Geriatric Trauma Care Using Social Network Analysis.

OBJECTIVE: To characterize hospital-level professional networks of physicians caring for older trauma patients as a function of trauma patient age distribution. BACKGROUND: The causal factors associated with between-hospital variation in geriatric trauma outcomes are poorly understood. Variation in physician practice patterns reflected by differences in professional networks might contribute to hospital-level differences in outcomes for older trauma patients. METHODS: This is a population-based, cross-sectional study of injured older adults (age 65 or above) and their physicians from January 1, 2014, to December 31, 2015, using Health Care Cost and Utilization Project inpatient data and Medicare claims from 158 hospitals in Florida. We used social network analyses to characterize the hospitals in terms of network density, cohesion, small-worldness, and heterogeneity, then used bivariate statistics to assess the relationship between network characteristics and hospital-level proportion of trauma patients who were aged 65 or above. RESULTS: We identified 107,713 older trauma patients and 169,282 patient-physician dyads. The hospital-level proportion of trauma patients who were aged 65 or above ranged from 21.5% to 89.1%. Network density, cohesion, and small-worldness in physician networks were positively correlated with hospital geriatric trauma proportions ( R =0.29, P <0.001; R =0.16, P =0.048; and R =0.19, P <0.001, respectively). Network heterogeneity was negatively correlated with geriatric trauma proportion ( R =0.40, P <0.001). CONCLUSIONS: Characteristics of professional networks among physicians caring for injured older adults are associated with the hospital-level proportion of trauma patients who are older, indicating differences in practice patterns at hospitals with older trauma populations. Associations between interspecialty collaboration and patient outcomes should be explored as an opportunity to improve the treatment of injured older adults.

Postdischarge Caregiver Burden Among Family Caregivers of Older Trauma Patients.

Importance: Caregiver burden, characterized by psychological distress and physical morbidity, affects more than 50 million family caregivers of older adults in the United States. Risk factors for caregiver burden among caregivers of older trauma patients have not been well characterized. Objective: To characterize postdischarge caregiver burden among caregivers of older trauma patients and identify targets that can inform interventions to improve their experience. Design, Setting, and Participants: This study used a repeated cross-sectional design. Participants were family caregivers for adults 65 years or older with traumatic injury who were discharged from 1 of 2 level I trauma centers. Telephone interviews were conducted at 1 month and 3 months postdischarge with family caregivers (identified by the patient as family or friends who provided unpaid care). Admissions occurred between December 2019 and May 2021, and data were analyzed from June 2021 to May 2022. Exposure: Hospital admission for geriatric trauma. Main Outcome and Measures: High caregiver burden was defined by a score of 17 or higher on the 12-item Zarit Burden Interview. Caregiver self-efficacy and preparedness for caregiving were assessed via the Revised Scale for Caregiving Self-Efficacy and Preparedness for Caregiving Scale, respectively. Associations between caregiver self-efficacy, preparedness for caregiving, and caregiver burden were tested via mixed-effect logistic regression. Results: There were 154 family caregivers enrolled in the study. Their mean (SD) age was 60.6 (13.0) years (range, 18-92 years), 108 of 154 were female (70.6%). The proportion of caregivers experiencing high burden (Zarit Burden Interview score ≥17) was unchanged over time (1 month, 38 caregivers [30.9%]; 3 months, 37 caregivers [31.4%]). Participants with lower caregiver self-efficacy and preparedness for caregiving were more likely to experience greater caregiver burden (odds ratio [OR], 7.79; 95% CI, 2.54-23.82; P < .001; and OR, 5.76; 95% CI, 1.86-17.88; P = .003, respectively). Conclusion and Relevance: This study found that nearly a third of family caregivers of older trauma patients experience high caregiver burden up to 3 months after the patients' discharge. Targeted interventions to increase caregiver self-efficacy and preparedness may reduce caregiver burden in geriatric trauma.

Surgical Utilization and Outcomes for Patients with Stage IV Melanoma in the Modern Immunotherapy Era.

BACKGROUND: The benefit of surgery for patients with stage IV melanoma in the modern era of effective immunotherapy is unclear. This study aimed to evaluate trends and outcomes after surgical resection of stage IV melanoma in the modern immunotherapy era. METHODS: Patients with stage IV melanoma who received surgery, immunotherapy, or both from 2012 to 2017 were identified from the National Cancer Database (NCDB). Demographics, facility-level characteristics, and use of immunotherapy were compared between patients who received surgery and those who did not. Multivariate Poisson regression modeling, Kaplan-Meier survival analysis, and Cox regression analysis were performed. RESULTS: The study identified 9800 patients with stage IV melanoma, and 2160 of these patients (22 %) underwent surgery. The patients who received surgery were more likely to be younger (P < 0.001), to have private insurance (P < 0.001), to have a higher median income (P = 0.008), and to receive treatment at academic/research programs (P < 0.001), whereas they were less likely to receive immunotherapy (33.7 % vs 36.6 %; P = 0.013). The patients who received immunotherapy had a lower likelihood of undergoing surgery (relative risk [RR], 0.82; 95 % confidence interval [CI[, 0.75-0.88; P < 0.001). The patients who received both surgery and immunotherapy had a better overall survival rate (hazard ratio [HR], 0.41; 95 % CI, 0.36-0.46; P < 0.01) than the patients who received neither immunotherapy nor surgery. CONCLUSIONS: The use of immunotherapy was associated with a lower use of surgery for patients with stage IV melanoma. The patients with stage IV disease who received both surgery and immunotherapy had the highest overall survival rates.

Association of Variation in US County-Level Rates of Liver Surgical Resection for Colorectal Liver Metastasis With Poverty Rates in 2010.

Importance: Among patients with colorectal liver metastasis (CRLM) who are eligible for curative-intent liver surgical resection, only half undergo liver metastasectomy. It is currently unclear how rates of liver metastasectomy vary geographically in the US. Geographic differences in county-level socioeconomic characteristics may, in part, explain variability in the receipt of liver metastasectomy for CRLM. Objective: To describe county-level variation in the receipt of liver metastasectomy for CRLM in the US and its association with poverty rates. Design, Setting, and Participants: This ecological, cross-sectional, and county-level analysis was conducted using data from the Surveillance, Epidemiology, and End Results Research Plus database. The study included the county-level proportion of patients who had colorectal adenocarcinoma diagnosed between January 1, 2010, and December 31, 2018, underwent primary surgical resection, and had liver metastasis without extrahepatic metastasis. The county-level proportion of patients with stage I colorectal cancer (CRC) was used as a comparator. Data analysis was performed on March 2, 2022. Exposures: County-level poverty in 2010 obtained from the US Census (proportion of county population below the federal poverty level). Main Outcomes and Measures: The primary outcome was county-level odds of liver metastasectomy for CRLM. The comparator outcome was county-level odds of surgical resection for stage I CRC. Multivariable binomial logistic regression accounting for clustering of outcomes within a county via an overdispersion parameter was used to estimate the county-level odds of receiving a liver metastasectomy for CRLM associated with a 10% increase in poverty rate. Results: In the 194 US counties included in this study, there were 11 348 patients. At the county level, the majority of the population was male (mean [SD], 56.9% [10.2%]), White (71.9% [20.0%]), and aged between 50 and 64 (38.1% [11.0%]) or 65 and 79 (33.6% [11.4%]) years. The adjusted odds of undergoing a liver metastasectomy was lower in counties with higher poverty in 2010 (per 10% increase; odds ratio, 0.82 [95% CI, 0.69-0.96]; P = .02). County-level poverty was not associated with receipt of surgery for stage I CRC. Despite the difference in rates of surgery (mean county-level rates were 0.24 for liver metastasectomy for CRLM and 0.75 for surgery for stage I CRC), the variance at the county-level for these 2 surgical procedures was similar (F370, 193 = 0.81; P = .08). Conclusions and Relevance: The findings of this study suggest that higher poverty was associated with lower receipt of liver metastasectomy among US patients with CRLM. Surgery for a more common and less complex cancer comparator (ie, stage I CRC) was not observed to be associated with county-level poverty rates. However, county-level variation in surgical rates was similar for CRLM and stage I CRC. These findings further suggest that access to surgical care for complex gastrointestinal cancers such as CRLM may be partially influenced by where patients live.

Medicaid expansion and surgery for HPB/GI cancers: NCDB difference-in-difference analysis.

BACKGROUND: It is unclear if Medicaid expansion improved access to surgical resection for hepatopancreatobiliary (HPB) and gastrointestinal (GI) cancers. METHODS: This was a quasi-experimental, cohort study using difference-in-difference analysis to evaluate differences in surgical resection for HPB/GI cancers in the post-Medicaid expansion era compared to the pre-Medicaid expansion era among patients residing in states that had Medicaid expansion versus not. RESULTS: During the pre- (2011-2013) and post-Medicaid expansion (2015-2017) eras, there were 49,954 patients between the ages of 40-64 who had liver cancer (n = 19,384; 38.8%), pancreatic cancer (n = 14,351; 28.7%), colorectal liver metastasis (n = 7566; 15.1%), or gastric cancer (n = 8653; 17.3%). 43.2% resided in expansion states (n = 21,577). There were no significant differences in the overall rates of surgical resection between expansion and non-expansion states before and after Medicaid expansion. CONCLUSIONS: Medicaid expansion did not impact surgical resection for HPB/GI cancers.

Implementing federal food service guidelines in federal and private worksite cafeterias in the United States leads to improved health outcomes and is cost saving.

Poor diet increases cardiometabolic disease risk, yet the impact of food service guidelines on employee health and its cost effectiveness is poorly understood. Federal food service guidelines (FFSG) aim to provide United States (U.S.) government employees with healthier food options. Using microsimulation modeling, we estimated changes in the incidence of cardiometabolic disease, related mortality, and the cost effectiveness of implementing FFSG in nationally representative model populations of government and private company employees across 5 years and lifetime. We based estimates on changes in workplace intake of six FFSG dietary targets and showed lifetime reductions of heart attacks (- 107/million), strokes (- 30/million), diabetes (- 134/million), ischemic heart disease deaths (- 56/million), and stroke deaths (- 8/million). FFSG is cost saving overall, with total savings in discounted healthcare costs from $4,611,026 (5 years) to $539,809,707 (lifetime) $U.S. This study demonstrates that FFSG improves health outcomes and is cost saving.

Epigenome-wide scan identifies differentially methylated regions for lung cancer using pre-diagnostic peripheral blood.

BACKGROUND: DNA methylation markers have been associated with lung cancer risk and may identify aetiologically relevant genomic regions, or alternatively, be markers of disease risk factors or biological processes associated with disease development. METHODS: In a nested case-control study, we measured blood leukocyte DNA methylation levels in pre-diagnostic samples collected from 430 participants (208 cases; 222 controls) in the 1989 CLUE II cohort. We compared DNA methylation levels with case/control status to identify novel genomic regions, both single CpG sites and differentially methylated regions (DMRs), while controlling for known DNA methylation changes associated with smoking using a previously described pack-years-based smoking methylation score. Stratification analyses were conducted over time from blood draw to diagnosis, histology, and smoking status. RESULTS: We identified 16 single CpG sites and 40 DMRs significantly associated with lung cancer risk (q < 0.05). The identified genomic regions were associated with genes including H19, HOXA3/HOXA4, RUNX3, BRICD5, PLXNB2, and RP13. For the single CpG sites, the strongest association was noted for cg09736286 in the DIABLO gene (OR [for 1 SD] = 2.99, 95% CI: 1.95-4.59, P-value = 4.81 × 10-7). We found that CpG sites in the HOXA3/HOXA4 region were hypermethylated in cases compared to controls. CONCLUSION: The single CpG sites and DMRs that we identified represented significant measurable differences in lung cancer risk, providing potential biomarkers for lung cancer risk stratification. Future studies will need to examine whether these regions are causally related to lung cancer.

Estimated economic burden of cancer associated with suboptimal diet in the United States.

PURPOSE: Suboptimal diet is a preventable cause of cancer. We aimed to estimate the economic burden of diet-associated cancer among US adults. METHODS: We used a Comparative Risk Assessment model to quantify the number of new cancer cases attributable to seven dietary factors among US adults ages 20 + years. A Markov cohort model estimated the 5-year medical costs for 15 diet-associated cancers diagnosed in 2015. We obtained dietary intake from 2013 to 2016 National Health and Nutrition Examination Survey, cancer incidence, and survival from 2008 to 2014 Surveillance, Epidemiology, and End Results (SEER) program, and medical costs from 2007 to 2013 linked SEER-Medicare data. RESULTS: The estimated 5-year medical costs of new diet-associated cancer cases diagnosed in 2015 were $7.44 (2018 US$). Colorectal cancer had the largest diet-related 5-year medical costs of $5.32B. Suboptimal consumption of whole grains ($2.76B), dairy ($1.82B), and high consumption of processed meats ($1.5B) accounted for the highest medical costs. Per-person medical costs attributable to suboptimal diet vary by gender, race, and age group. CONCLUSIONS: Suboptimal diet contributes substantially to the economic burden of diet-associated cancers among US adults. This study highlights the need to implement population-based strategies to improve diet and reduce cancer burden in the US.

Methylation-derived inflammatory measures and lung cancer risk and survival.

BACKGROUND: Examining immunity-related DNA methylation alterations in blood could help elucidate the role of the immune response in lung cancer etiology and aid in discovering factors that are key to lung cancer development and progression. In a nested, matched case-control study, we estimated methylation-derived NLR (mdNLR) and quantified DNA methylation levels at loci previously linked with circulating concentrations of C-reactive protein (CRP). We examined associations between these measures and lung cancer risk and survival. RESULTS: Using conditional logistic regression and further adjusting for BMI, batch effects, and a smoking-based methylation score, we observed a 47% increased risk of non-small cell lung cancer (NSCLC) for one standard deviation (SD) increase in mdNLR (n = 150 pairs; OR: 1.47, 95% CI 1.08, 2.02). Using a similar model, the estimated CRP Scores were inversely associated with risk of NSCLC (e.g., Score 1 OR: 0.57, 95% CI: 0.40, 0.81). Using Cox proportional hazards models adjusting for age, sex, smoking status, methylation-predicted pack-years, BMI, batch effect, and stage, we observed a 28% increased risk of dying from lung cancer (n = 145 deaths in 205 cases; HR: 1.28, 95% CI: 1.09, 1.50) for one SD increase in mdNLR. CONCLUSIONS: Our study demonstrates that immunity status measured with DNA methylation markers is associated with lung cancer a decade or more prior to cancer diagnosis. A better understanding of immunity-associated methylation-based biomarkers in lung cancer development could provide insight into critical pathways.

Two-Sample Mendelian Randomization Analysis of Associations Between Periodontal Disease and Risk of Cancer.

Background: Observational studies indicate that periodontal disease may increase the risk of colorectal, lung, and pancreatic cancers. Using a 2-sample Mendelian randomization (MR) analysis, we assessed whether a genetic predisposition index for periodontal disease was associated with colorectal, lung, or pancreatic cancer risks. Methods: Our primary instrument included single nucleotide polymorphisms with strong genome-wide association study evidence for associations with chronic, aggressive, and/or severe periodontal disease (rs729876, rs1537415, rs2738058, rs12461706, rs16870060, rs2521634, rs3826782, and rs7762544). We used summary-level genetic data for colorectal cancer (n = 58 131 cases; Genetics and Epidemiology of Colorectal Cancer Consortium, Colon Cancer Family Registry, and Colorectal Transdisciplinary Study), lung cancer (n = 18 082 cases; International Lung Cancer Consortium), and pancreatic cancer (n = 9254 cases; Pancreatic Cancer Consortia). Four MR approaches were employed for this analysis: random-effects inverse-variance weighted (primary analyses), Mendelian Randomization-Pleiotropy RESidual Sum and Outlier, simple median, and weighted median. We conducted secondary analyses to determine if associations varied by cancer subtype (colorectal cancer location, lung cancer histology), sex (colorectal and pancreatic cancers), or smoking history (lung and pancreatic cancer). All statistical tests were 2-sided. Results: The genetic predisposition index for chronic or aggressive periodontitis was statistically significantly associated with a 3% increased risk of colorectal cancer (per unit increase in genetic index of periodontal disease; P = .03), 3% increased risk of colon cancer (P = .02), 4% increased risk of proximal colon cancer (P = .01), and 3% increased risk of colorectal cancer among females (P = .04); however, it was not statistically significantly associated with the risk of lung cancer or pancreatic cancer, overall or within most subgroups. Conclusions: Genetic predisposition to periodontitis may be associated with colorectal cancer risk. Further research should determine whether increased periodontitis prevention and increased cancer surveillance of patients with periodontitis is warranted.

DNA methylation ageing clocks and pancreatic cancer risk: pooled analysis of three prospective nested case-control studies.

DNA methylation (DNAm) age may reflect age-related variations in biological changes and abnormalities related to ageing. DNAm age acceleration measures have been associated with a number of cancers, but to our knowledge, have not been examined in relation to pancreatic cancer risk or survival. DNAm levels in leukocytes of prediagnostic blood samples of 393 pancreatic cancer cases and 431 matched controls, pooled from three large prospective cohort studies, were used to estimate DNAm age, epigenetic age acceleration (AA), and intrinsic epigenetic age acceleration (IEAA) metrics. Logistic regression and Cox proportional hazard regression models were used to examine the relationship between the various AA and IEAA metrics and pancreatic cancer risk and survival, respectively. The results showed that pancreatic cancer risk was significantly increased across all IEAA metrics, ranging from 83% to 95% increased risk when comparing the third and highest quartiles to the lowest quartile of IEAA. Consistent with these findings, the results from multivariate spline regression analyses showed non-linear relationships between all three IEAA metrics and pancreatic cancer risk with apparent threshold effect including two turning points at minimal and at maximal risks, respectively. There is no evidence of a significant association between pancreatic cancer survival and any of the epigenetic AA or IEAA metrics. Our results indicate DNAm age acceleration, measured in blood prior to cancer diagnosis, is associated with an increased risk of pancreatic cancer in a complex nonlinear, dose-response manner. Epigenetic IEAA metrics may be a useful addition to current methods for pancreatic cancer risk prediction.

Plant- and animal-based diet quality and mortality among US adults: a cohort study.

Not all plant-based and animal foods exert the same health effects due to their various nutrient compositions. We aimed to assess the quality of plant-based v. animal foods in relation to mortality in a prospective cohort study. Using data collected from a nationally representative sample of 36 825 adults in the National Health and Nutrition Examination Survey 1999-2014, we developed a de novo Comprehensive Diet Quality Index (cDQI) that assesses the quality of seventeen foods based on the healthfulness and separately scored the quality of eleven plant-based foods in a plant-based Diet Quality Index (pDQI) and six animal foods in an animal-based Diet Quality Index (aDQI). Mortality from all causes, heart disease and cancer were obtained from linkage to the National Death Index up to 31 December 2015. Cox proportional hazard models were used to estimate hazard ratios (HR) and 95 % CI after multivariable adjustments. During a median follow-up of 8·3 years, 4669 all-cause deaths occurred, including 798 deaths due to heart disease and 1021 due to cancer. Compared with individuals in the lowest quartile, those in the highest quartile of cDQI had a lower risk of all-cause mortality (HR 0·75, 95 % CI 0·65, 0·86; Ptrend < 0·001), which largely reflected the inverse relationship between quality of plant-based foods (pDQI) and all-cause mortality (HR 0·66, 95 % CI 0·58, 0·74; Ptrend < 0·001). No independent association was found for the quality of animal foods (aDQI) and mortality. Our results suggest that consuming healthy plant-based foods is associated with lower all-cause mortality among US adults.

Vitamin D and Calcium in Children 0-36 Months: A Scoping Review of Health Outcomes.

METHODS: Updated literature searches were conducted across 5 electronic databases to identify all randomized controlled trials, cohort studies, nested case-control or case-cohort studies, and systematic reviews published after the 2009 U.S. Agency for Healthcare Research and Quality's (AHRQ) evidence report, Vitamin D and Calcium: a Systematic Review of Health Outcomes. In total, 65 studies were summarized and analyzed in the present review. RESULTS: There was a steady increasing trend in the number of publications reporting outcomes related to skeletal health, growth, and infectious disease from 2008 to 2019, although the number of published vitamin D studies was much larger than calcium studies. CONCLUSIONS: The data presented in this review can facilitate assessment of the variety of outcomes and the amount of potentially useful literature available for each outcome. The results of this scoping review can be used to guide the undertaking of the subsequent systematic reviews.

Epigenome-Wide Association Study Using Prediagnostic Bloods Identifies New Genomic Regions Associated With Pancreatic Cancer Risk.

BACKGROUND: Epigenome-wide association studies using peripheral blood have identified specific sites of DNA methylation associated with risk of various cancers and may hold promise to identify novel biomarkers of risk; however, few studies have been performed for pancreatic cancer and none using a prospective study design. METHODS: Using a nested case-control study design, incident pancreatic cancer cases and matched controls were identified from participants who provided blood at baseline in 3 prospective cohort studies. DNA methylation levels were measured in DNA extracted from leukocytes using the Illumina MethylationEPIC array. Average follow-up period for this analysis was 13 years. RESULTS: Several new genomic regions were identified as being differentially methylated in cases and controls; the 5 strongest associations were observed for CpGs located in genes TMEM204/IFT140, MFSD6L, FAM134B/RETREG1, KCNQ1D, and C6orf227. For some CpGs located in chromosome 16p13.3 (near genes TMEM204 and IFT140), associations were stronger with shorter time to diagnosis (eg, odds ratio [OR] = 5.95, 95% confidence interval [CI] = 1.52 to 23.12, for top vs bottom quartile, for <5 years between blood draw and cancer diagnosis), but associations remained statistically significantly higher even when cases were diagnosed over 10 years after blood collection. Statistically significant differences in DNA methylation levels were also observed in the gastric secretion pathway using Gene Set Enrichment Analysis (GSEA) analysis. CONCLUSIONS: Changes in DNA methylation in peripheral blood may mark alterations in metabolic or immune pathways that play a role in pancreatic cancer. Identifying new biological pathways in carcinogenesis of pancreatic cancer using epigenome-wide association studies approach could provide new opportunities for improving treatment and prevention.

DNA Methylation-Derived Immune Cell Profiles, CpG Markers of Inflammation, and Pancreatic Cancer Risk.

BACKGROUND: Pancreatic cancer is projected to become the second most common cause of cancer-related death over the next 5 years. Because inflammation is thought to be a common trajectory for disease initiation, we sought to prospectively characterize immune profiles using DNA methylation markers and examine DNA methylation levels previously linked to inflammation biomarkers to evaluate whether these immune markers play a key role in pancreatic cancer. METHODS: In a nested case-control study pooling three U.S. prospective cohort studies, DNA methylation was measured in prediagnostic leukocytes of incident pancreatic cancer cases and matched controls using the Illumina MethylationEPIC array. Differentially methylated regions were used to predict immune cell types, and CpGs previously associated with inflammatory biomarkers were selected for the analysis. DNA methylation data from a retrospective case-control study conducted in Spain (PanGenEU) was used for independent replication. RESULTS: Immune cell proportions and ratio of cell proportions were not associated with pancreatic cancer risk in the nested case-control study. Methylation extent of CpGs residing in or near gene MNDA was significantly associated with pancreatic cancer risk in the nested case-control study and replicated in PanGenEU. Methylation level of a promoter CpG of gene PIM-1 was associated with survival in both studies. CONCLUSIONS: Using a targeted approach, we identified several CpGs that may play a role in pancreatic carcinogenesis in two large, independent studies with distinct study designs. IMPACT: These findings could provide insight into critical pathways that may help identify new markers of early disease and survival.

Dietary Supplement Use among Adult Cancer Survivors in the United States.

BACKGROUND: Many cancer patients initiate dietary supplement use after cancer diagnosis. How dietary supplement use contributes to the total nutrient intake among cancer survivors as compared with individuals without cancer needs to be determined. OBJECTIVES: We aimed to evaluate nutrient intakes from dietary supplements among cancer survivors in relation to their total nutrient intake and compare those with individuals without cancer. METHODS: We evaluated the prevalence, dose, and reason for using dietary supplements among 2772 adult cancer survivors and 31,310 individuals without cancer who participated in the NHANES 2003-2016. RESULTS: Cancer survivors reported a higher prevalence of any (70.4% vs. 51.2%) and multivitamin/mineral (48.9% vs. 36.6%) supplement use and supplement use of 11 individual vitamins and 8 minerals than individuals without cancer. Overall, cancer survivors had significantly higher amounts of nutrient intake from supplements but lower nutrient intakes from foods for the majority of the nutrients. Compared with individuals without cancer, cancer survivors had a higher percentage of individuals with inadequate intake (total nutrient intake 

Cost-Effectiveness of a National Sugar-Sweetened Beverage Tax to Reduce Cancer Burdens and Disparities in the United States.

BACKGROUND: Sugar-sweetened beverage (SSB) consumption contributes to obesity, a risk factor for 13 cancers. Although SSB taxes can reduce intake, the health and economic impact on reducing cancer burdens in the United States are unknown, especially among low-income Americans with higher SSB intake and obesity-related cancer burdens. METHODS: We used the Diet and Cancer Outcome Model, a probabilistic cohort state-transition model, to project health gains and economic benefits of a penny-per-ounce national SSB tax on reducing obesity-associated cancers among US adults aged 20 years and older by income. RESULTS: A national SSB tax was estimated to prevent 22 075 (95% uncertainty interval [UI] = 16 040-28 577) new cancer cases and 13 524 (95% UI = 9841-17 681) cancer deaths among US adults over a lifetime. The policy was estimated to cost $1.70 (95% UI = $1.50-$1.95) billion for government implementation and $1.70 (95% UI = $1.48-$1.96) billion for industry compliance, while saving $2.28 (95% UI = $1.67-$2.98) billion cancer-related healthcare costs. The SSB tax was highly cost-effective from both a government affordability perspective (incremental cost-effectiveness ratio [ICER] = $1486, 95% UI = -$3516-$9265 per quality-adjusted life year [QALY]) and a societal perspective (ICER = $13 220, 95% UI = $3453-$28 120 per QALY). Approximately 4800 more cancer cases and 3100 more cancer deaths would be prevented, and $0.34 billion more healthcare cost savings would be generated among low-income (federal poverty-to-income ratio [FPIR] ≤ 1.85) than higher-income individuals (FPIR > 1.85). CONCLUSIONS: A penny-per-ounce national SSB tax is cost-effective for cancer prevention in the United States, with the largest health gains and economic benefits among low-income Americans.

Trends in Dietary Carbohydrate, Protein, and Fat Intake and Diet Quality Among US Adults, 1999-2016.

Importance: Changes in the economy, nutrition policies, and food processing methods can affect dietary macronutrient intake and diet quality. It is essential to evaluate trends in dietary intake, food sources, and diet quality to inform policy makers. Objective: To investigate trends in dietary macronutrient intake, food sources, and diet quality among US adults. Design, Setting, and Participants: Serial cross-sectional analysis of the US nationally representative 24-hour dietary recall data from 9 National Health and Nutrition Examination Survey cycles (1999-2016) among adults aged 20 years or older. Exposure: Survey cycle. Main Outcomes and Measures: Dietary intake of macronutrients and their subtypes, food sources, and the Healthy Eating Index 2015 (range, 0-100; higher scores indicate better diet quality; a minimal clinically important difference has not been defined). Results: There were 43 996 respondents (weighted mean age, 46.9 years; 51.9% women). From 1999 to 2016, the estimated energy from total carbohydrates declined from 52.5% to 50.5% (difference, -2.02%; 95% CI, -2.41% to -1.63%), whereas that of total protein and total fat increased from 15.5% to 16.4% (difference, 0.82%; 95% CI, 0.67%-0.97%) and from 32.0% to 33.2% (difference, 1.20%; 95% CI, 0.84%-1.55%), respectively (all P < .001 for trend). Estimated energy from low-quality carbohydrates decreased by 3.25% (95% CI, 2.74%-3.75%; P < .001 for trend) from 45.1% to 41.8%. Increases were observed in estimated energy from high-quality carbohydrates (by 1.23% [95% CI, 0.84%-1.61%] from 7.42% to 8.65%), plant protein (by 0.38% [95% CI, 0.28%-0.49%] from 5.38% to 5.76%), saturated fatty acids (by 0.36% [95% CI, 0.20%-0.51%] from 11.5% to 11.9%), and polyunsaturated fatty acids (by 0.65% [95% CI, 0.56%-0.74%] from 7.58% to 8.23%) (all P < .001 for trend). The estimated overall Healthy Eating Index 2015 increased from 55.7 to 57.7 (difference, 2.01; 95% CI, 0.86-3.16; P < .001 for trend). Trends in high- and low-quality carbohydrates primarily reflected higher estimated energy from whole grains (0.65%) and reduced estimated energy from added sugars (-2.00%), respectively. Trends in plant protein were predominantly due to higher estimated intake of whole grains (0.12%) and nuts (0.09%). Conclusions and Relevance: From 1999 to 2016, US adults experienced a significant decrease in percentage of energy intake from low-quality carbohydrates and significant increases in percentage of energy intake from high-quality carbohydrates, plant protein, and polyunsaturated fat. Despite improvements in macronutrient composition and diet quality, continued high intake of low-quality carbohydrates and saturated fat remained.