Risk of Potentially Preventable Hospitalizations After SARS-CoV-2 Infection.

Importance: Research demonstrates that SARS-CoV-2 infection is associated with increased risk of all-cause hospitalization. However, no prior studies have assessed the association between SARS-CoV-2 and potentially preventable hospitalizations-that is, hospitalizations for conditions that can usually be effectively managed in ambulatory care settings. Objective: To examine whether SARS-CoV-2 is associated with potentially preventable hospitalization in a nationwide cohort of US veterans. Design, Setting, and Participants: This cohort study used an emulated target randomized trial design with monthly sequential trials to compare risk of a potentially preventable hospitalization among veterans with SARS-CoV-2 and matched comparators without SARS-CoV-2. A total of 189 136 US veterans enrolled in the Veterans Health Administration (VHA) who were diagnosed with SARS-CoV-2 between March 1, 2020, and April 30, 2021, and 943 084 matched comparators were included in the analysis. Data were analyzed from May 10, 2023, to January 26, 2024. Exposure: SARS-CoV-2 infection. Main Outcomes and Measures: The primary outcome was a first potentially preventable hospitalization in VHA facilities, VHA-purchased community care, or Medicare fee-for-service care. Extended Cox models were used to examine adjusted hazard ratios (AHRs) of potentially preventable hospitalization among veterans with SARS-CoV-2 and comparators during follow-up periods of 0 to 30, 0 to 90, 0 to 180, and 0 to 365 days. The start of follow-up was defined as the date of each veteran's first positive SARS-CoV-2 diagnosis, with the same index date applied to their matched comparators. Results: The 1 132 220 participants were predominantly men (89.06%), with a mean (SD) age of 60.3 (16.4) years. Most veterans were of Black (23.44%) or White (69.37%) race. Veterans with SARS-CoV-2 and comparators were well-balanced (standardized mean differences, all <0.100) on observable baseline clinical and sociodemographic characteristics. Overall, 3.10% of veterans (3.81% of those with SARS-CoV-2 and 2.96% of comparators) had a potentially preventable hospitalization during 1-year follow-up. Risk of a potentially preventable hospitalization was greater among veterans with SARS-CoV-2 than comparators in 4 follow-up periods: 0- to 30-day AHR of 3.26 (95% CI, 3.06-3.46); 0- to 90-day AHR of 2.12 (95% CI, 2.03-2.21); 0- to 180-day AHR of 1.69 (95% CI, 1.63-1.75); and 0- to 365-day AHR of 1.44 (95% CI, 1.40-1.48). Conclusions and Relevance: In this cohort study, an increased risk of preventable hospitalization in veterans with SARS-CoV-2, which persisted for at least 1 year after initial infection, highlights the need for research on ways in which SARS-CoV-2 shapes postinfection care needs and engagement with the health system. Solutions are needed to mitigate preventable hospitalization after SARS-CoV-2.

Vegetarian diets and risk of all-cause mortality in a population-based prospective study in the United States.

The popularity of vegetarian diets has increased the need for studies on long-term health outcomes. A limited number of studies, including only one study from a non-vegetarian population, investigated the risk of mortality with self-identified vegetarianism and reported inconsistent results. This study evaluated prospective associations between vegetarian diets and all-cause mortality among 117,673 participants from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial cohort study. Vegetarian diet status was self-identified on the questionnaire. Deaths were ascertained from follow-up questionnaires and the National Death Index database. Multivariable Cox regression models were used to estimate the risk of all-cause mortality in hazard ratio (HR) and 95% confidence intervals (CI). By diet group, there were 116,894 omnivores (whose diet does not exclude animal products), 329 lacto- and/or ovo-vegetarians (whose diet excludes meat, but includes dairy and/or eggs), 310 pesco-vegetarians (whose diet excludes meat except for fish and seafood) and 140 vegans (whose diet excludes all animal products). After an average follow-up of 18 years, 39,763 participants were deceased. The risk of all-cause mortality did not statistically significantly differ among the four diet groups. Comparing with the omnivore group, the HR (95% CI) were 0.81 (0.64-1.03) for pesco-vegetarian group, 0.99 (0.80-1.22) for lacto- and/or ovo-vegetarian group and 1.27 (0.99-1.63) for vegan group, respectively. Similarly, mortality risk did not differ when comparing lacto- and/or ovo-vegetarians plus vegans with meat/fish eaters (omnivores and pesco-vegetarians) (HR [95% CI] = 1.09 [0.93-1.28]). As this study is one of the two studies of vegetarianism and mortality in non-vegetarian populations, further investigation is warranted.

Dairy product consumption and lung cancer risk: A prospective analysis.

BACKGROUND & AIM: Current evidence on prospective associations between dairy product, dairy fat and lactose intakes and lung cancer risk is limited and inconsistent. We conducted a prospective analysis of associations of lung cancer risk with dairy product intakes in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) cohort. METHODS: Pre-diagnostic dairy product intake was assessed through a validated Diet History Questionnaire. All incident lung cancer cases were pathologically verified. Multivariable Cox regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for associations of lung cancer risk with intakes of total, full-fat, low-fat dairy, fermented or non-fermented dairy products; milk fat content preference; and intakes of total and saturated fats and lactose from dairy products. RESULTS: Among 101,709 adults (mean age of 65.5 years), a total of 1583 lung cancer cases were identified during 1,167,239 person-years of follow up. Mean total dairy product intake was 156 g/1000 kilocalories (kcal), including 20 g/1000 kcal from fermented dairy products. Total dairy intake was not associated with lung cancer risk (HR [95% CI] = 1.03 [0.89-1.18]) comparing the highest quartile with the lowest. Fermented dairy intake was inversely associated with lung cancer risk (0.85 [0.72-0.99]). In contrast, there were no statistically significant associations with low-fat, full-fat or non-fermented dairy product intakes. The preference of whole milk when consuming milk as beverage was associated with a higher risk of lung cancer than the preference of <0.5% fat milk (1.24 [1.03-1.49]). Total fat, saturated fat and lactose intakes from dairy products each were not associated with lung cancer risk. CONCLUSIONS: Our results suggest an inverse association of lung cancer risk with fermented dairy intake and a positive association with the whole milk preference in a US population. Future studies exploring underlying molecular mechanisms are warranted.

Calcium Intake and Lung Cancer Risk: A Pooled Analysis of 12 Prospective Cohort Studies.

BACKGROUND: Previous studies on calcium intake and lung cancer risk reported inconsistent associations, possibly due to the differences in intake amounts and contributing sources of calcium and smoking prevalence. OBJECTIVES: We investigated the associations of lung cancer risk with intake of calcium from foods and/or supplements and major calcium-rich foods in 12 studies. METHODS: Data from 12 prospective cohort studies conducted in the United States, Europe, and Asia were pooled and harmonized. We applied the DRI to categorize calcium intake based on the recommendations and quintile distribution to categorize calcium-rich food intake. We ran multivariable Cox regression by each cohort and pooled risk estimates to compute overall HR (95% CI). RESULTS: Among 1,624,244 adult men and women, 21,513 incident lung cancer cases were ascertained during a mean follow-up of 9.9 y. Overall, the dietary calcium intake was not significantly associated with lung cancer risk; the HRs (95% CI) were 1.08 (0.98-1.18) for higher (>1.5 RDA) and 1.01 (0.95-1.07) for lower intake (<0.5 RDA) comparing with recommended intake (EAR to RDA). Milk and soy food intake were positively or inversely associated with lung cancer risk [HR (95% CI) = 1.07 (1.02-1.12) and 0.92 (0.84-1.00)], respectively. The positive association with milk intake was significant only in European and North American studies (P-interaction for region = 0.04). No significant association was observed for calcium supplements. CONCLUSIONS: In this largest prospective investigation, overall, calcium intake was not associated with risk of lung cancer, but milk intake was associated with a higher risk. Our findings underscore the importance of considering food sources of calcium in studies of calcium intake.

Dietary Effects on Pain Symptoms in Patients with Fibromyalgia Syndrome: Systematic Review and Future Directions.

Fibromyalgia syndrome (FMS) is recognized for its difficulty to diagnose and its subjective symptomatology. There is neither a known cure nor a recommended therapeutic diet to aid in the multidisciplinary treatment. We conducted a systematic review to investigate if diets can improve pain symptoms of fibromyalgia. Through the PubMed search in March 2022, 126 abstracts were identified. We included both intervention and observational studies of diets and pain symptoms among patients with FMS. After screening titles, abstracts, and full-texts, 12 studies, including 11 intervention and one observational study, were selected. These studies included 546 participants and investigated plant-based diets (n = 3), anti-inflammatory diets (n = 1), gluten-free diets (n = 2), and elimination/restrictive diets (n = 6). These studies assessed pain symptoms through visual analogue scale for pain, fibromyalgia impact questionnaire/revised fibromyalgia impact questionnaire, tender point count, pain pressure threshold, and/or total myalgic score. Nine studies, including all three plant-based diet studies, reported statistically significant beneficial effects of their respective diets on pain symptom measurements. Given the small sample size and short intervention duration of the included studies, limited evidence currently exists to recommend any specific diet to patients with FMS. Further research is warranted to clarify specific diets to recommend and explore their potential mechanisms.

Cardiovascular Disease and Health-Related Quality of Life Among Asian American, Native Hawaiian and Pacific Islander Older Adults.

Objectives: Assess the relationship between cardiovascular disease (CVD) and health-related quality of life (HRQOL) among Asian American, Native Hawaiian, and Pacific Islander (NH/PI) compared to white older adults. Methods: Data were from the 2011-2015 Health Outcomes Survey. HRQOL was assessed using the Veterans RAND 12-Item Survey, composed of physical (PCS) and mental component scores (MCS). Lower scores represent worse health. Multivariate regression was conducted to estimate PCS and MCS mean score differences related to self-reported CVD (coronary artery disease, congestive heart failure, myocardial infarction, other heart conditions, stroke) and race/ethnicity. Results: There were marked differences in PCS and MCS scores by disaggregated Asian American and NH/PI subgroups. After adjustment, Asian American and NH/PI older adults had better PCS but worse MCS than white older adults. Race/ethnicity moderated the relationship between CVD and HRQOL. Discussion: Asian American and NH/PI older adults with CVD had poorer mental health compared to their white counterparts.

Prediagnosis Leisure-Time Physical Activity and Lung Cancer Survival: A Pooled Analysis of 11 Cohorts.

BACKGROUND: Little is known about the association between physical activity before cancer diagnosis and survival among lung cancer patients. In this pooled analysis of 11 prospective cohorts, we investigated associations of prediagnosis leisure-time physical activity (LTPA) with all-cause and lung cancer-specific mortality among incident lung cancer patients. METHODS: Using self-reported data on regular engagement in exercise and sports activities collected at study enrollment, we assessed metabolic equivalent hours (MET-h) of prediagnosis LTPA per week. According to the Physical Activity Guidelines for Americans, prediagnosis LTPA was classified into inactivity, less than 8.3 and at least 8.3 MET-h per week (the minimum recommended range). Cox regression was used to estimate hazard ratios (HRs) and 95% confidence interval (CIs) for all-cause and lung cancer-specific mortality after adjustment for major prognostic factors and lifetime smoking history. RESULTS: Of 20 494 incident lung cancer patients, 16 864 died, including 13 596 deaths from lung cancer (overall 5-year relative survival rate = 20.9%, 95% CI = 20.3% to 21.5%). Compared with inactivity, prediagnosis LTPA of more than 8.3 MET-h per week was associated with a lower hazard of all-cause mortality (multivariable-adjusted HR = 0.93, 95% CI = 0.88 to 0.99), but not with lung cancer-specific mortality (multivariable-adjusted HR = 0.99, 95% CI = 0.95 to 1.04), among the overall population. Additive interaction was found by tumor stage (Pinteraction = .008 for all-cause mortality and .003 for lung cancer-specific mortality). When restricted to localized cancer, prediagnosis LTPA of at least 8.3 MET-h per week linked to 20% lower mortality: multivariable-adjusted HRs were 0.80 (95% CI = 0.67 to 0.97) for all-cause mortality and 0.80 (95% CI = 0.65 to 0.99) for lung cancer-specific mortality. CONCLUSIONS: Regular participation in LTPA that met or exceeded the minimum Physical Activity Guidelines was associated with reduced hazards of mortality among lung cancer patients, especially those with early stage cancer.

Trends in Cardiovascular Disease by Asian American, Native Hawaiian, and Pacific Islander Ethnicity, Medicare Health Outcomes Survey 2011-2015.

BACKGROUND: The burden of cardiovascular disease (CVD) is increasing in the aging population. However, little is known about CVD risk factors and outcomes for Asian American, Native Hawaiian, and Other Pacific Islander (NH/PI) older adults by disaggregated subgroups. METHODS: Data were from the Centers for Medicare and Medicaid Services 2011-2015 Health Outcomes Survey, which started collecting expanded racial/ethnic data in 2011. Guided by Andersen and Newman's theoretical framework, multivariable logistic regression analyses were conducted to examine the prevalence and determinants of CVD risk factors (obesity, diabetes, smoking status, hypertension) and CVD conditions (coronary artery disease [CAD], congestive heart failure [CHF], myocardial infarction [MI], other heart conditions, stroke) for 10 Asian American and NH/PI subgroups and White adults. RESULTS: Among the 639 862 respondents, including 26 853 Asian American and 4 926 NH/PI adults, 13% reported CAD, 7% reported CHF, 10% reported MI, 22% reported other heart conditions, and 7% reported stroke. CVD risk factors varied by Asian American and NH/PI subgroup. The prevalence of overweight, obesity, diabetes, and hypertension was higher among most Asian American and NH/PI subgroups than White adults. After adjustment, Native Hawaiians had significantly greater odds of reporting stroke than White adults. CONCLUSIONS: More attention should focus on NH/PIs as a priority population based on the disproportionate burden of CVD risk factors compared with their White and Asian American counterparts. Future research should disaggregate racial/ethnic data to provide accurate depictions of CVD and investigate the development of CVD risk factors in Asian Americans and NH/PIs over the life course.

Diet and PPARG2 Pro12Ala Polymorphism Interactions in Relation to Cancer Risk: A Systematic Review.

Peroxisome proliferator-activated receptor-γ2 gene Pro12Ala allele polymorphism (PPARG2 Pro12Ala; rs1801282) has been linked to both cancer risk and dietary factors. We conducted the first systematic literature review of studies published before December 2020 using the PubMed database to summarize the current evidence on whether dietary factors for cancer may differ by individuals carrying C (common) and/or G (minor) alleles of the PPARG2 Pro12Ala allele polymorphism. The inclusion criteria were observational studies that investigated the association between food or nutrient consumption and risk of incident cancer stratified by PPARG2 Pro12Ala allele polymorphism. From 3815 identified abstracts, nine articles (18,268 participants and 4780 cancer cases) covering three cancer sites (i.e., colon/rectum, prostate, and breast) were included. CG/GG allele carriers were more impacted by dietary factors than CC allele carriers. High levels of protective factors (e.g., carotenoids and prudent dietary patterns) were associated with a lower cancer risk, and high levels of risk factors (e.g., alcohol and refined grains) were associated with a higher cancer risk. In contrast, both CG/GG and CC allele carriers were similarly impacted by dietary fats, well-known PPAR-γ agonists. These findings highlight the complex relation between PPARG2 Pro12Ala allele polymorphism, dietary factors, and cancer risk, which warrant further investigation.

Associations of coffee and tea consumption with lung cancer risk.

Associations of coffee and tea consumption with lung cancer risk have been inconsistent, and most lung cancer cases investigated were smokers. Included in this study were over 1.1 million participants from 17 prospective cohorts. Cox regression analyses were conducted to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Potential effect modifications by sex, smoking, race, cancer subtype and coffee type were assessed. After a median 8.6 years of follow-up, 20 280 incident lung cancer cases were identified. Compared with noncoffee and nontea consumption, HRs (95% CIs) associated with exclusive coffee drinkers (≥2 cups/d) among current, former and never smokers were 1.30 (1.15-1.47), 1.49 (1.27-1.74) and 1.35 (1.15-1.58), respectively. Corresponding HRs for exclusive tea drinkers (≥2 cups/d) were 1.16 (1.02-1.32), 1.10 (0.92-1.32) and 1.37 (1.17-1.61). In general, the coffee and tea associations did not differ significantly by sex, race or histologic subtype. Our findings suggest that higher consumption of coffee or tea is associated with increased lung cancer risk. However, these findings should not be assumed to be causal because of the likelihood of residual confounding by smoking, including passive smoking, and change of coffee and tea consumption after study enrolment.

The Association Between Food-Away-From-Home Frequency and a Higher BMI Varies by Food Security Status in US Adults.

BACKGROUND: For decades, Americans have increasingly relied on food away from home (FAFH) despite its association with negative health outcomes. Little is known about FAFH frequency and expenditures of adults with lower food security (FS) and their association with health outcomes, such as BMI. OBJECTIVES: We evaluated patterns of adults' FAFH purchases by FS status and other demographic characteristics, and examined the association between FAFH frequency and BMI in adults of varying levels of FS. METHODS: This cross-sectional study used data from the Consumer Behavior Survey, Food Security Survey, and anthropometric measurements to assess FAFH frequency and expenditures, FS, and calculated BMI of adults (≥18 y) who participated in the NHANES 2007-2014 (n = 20,733). We used multinomial logistic regression to examine the association between FAFH frequency quartiles (quartile 1: 0 n/wk; quartile 2: 1-2 n/wk; quartile 3: 3-4 n/wk; quartile 4: ≥5 n/wk) and BMI by FS category. RESULTS: Although FAFH frequency was similar across FS levels, adults with high FS spent more dollars (${\$}$213.60) and a greater proportion (29.4%) of their food budget on FAFH compared with adults with marginal, low, and very low FS (${\$}$133.00, ${\$}$116.20, ${\$}$103.30 and 21.4%, 19.7%, 20.0%, respectively). Obesity prevalence was highest in adults with low FS (42.9%) and very low FS (41.5%), and lowest in adults with high FS (33.7%). FAFH frequency and BMI were positively associated in adults with high (P < 0.001), marginal (P = 0.025), and low (P = 0.024) FS, but not in adults with very low FS (P = 0.589). CONCLUSIONS: FAFH is frequent in adults regardless of FS status. The positive association between FAFH and BMI is the strongest in adults with high FS, the group with the lowest prevalence of obesity. Conversely, BMI was not associated with FAFH in adults with very low FS, despite their higher prevalence of obesity.

Coffee Consumption and C-Reactive Protein Levels: A Systematic Review and Meta-Analysis.

Coffee contains bioactive compounds with anti-inflammatory properties, and its consumption may reduce c-reactive protein (CRP) levels, a biomarker of chronic inflammation. A previous meta-analysis reported no overall association between blood CRP level and coffee consumption by modeling the coffee consumption in categories, with substantial heterogeneity. However, the coffee cup volume was not considered. We conducted a systematic review and dose-response meta-analysis investigating the association between coffee consumption and CRP levels reported in previous observational studies. A dose-response meta-analysis was conducted by mixed-effects meta-regression models using the volume of coffee consumed as metric. Eleven studies from three continents were identified using the PubMed database, totaling 61,047 participants. Three studies with the largest sample sizes observed a statistically significant association between coffee and CRP levels, which was inverse among European and United States (US) women and Japanese men (1.3%-5.5% decrease in CRP per 100 mL of coffee consumed) and positive among European men (2.2% increase). Other studies showed no statistically significant associations. When all studies were combined in the dose-response meta-analysis, no statistically significant associations were observed among all participants or when stratified by gender or geographic location, reflecting the conflicting associations reported in the included studies. Further studies are warranted to explore these inconsistent associations.

Legume Consumption Patterns in US Adults: National Health and Nutrition Examination Survey (NHANES) 2011-2014 and Beans, Lentils, Peas (BLP) 2017 Survey.

Given the emerging health benefits of regular legume consumption, we hypothesized that the historically low legume consumption levels in US adults increased. We evaluated legume consumption patterns in US adults using cross-sectional data from the 2011-2012 and 2013-2014-year cycles of National Health and Nutrition Examination Surveys (NHANES) and a 2017 cross-sectional, online survey of Oregon families named "Beans, Lentils, Peas (BLP) Survey". We also compared legume consumption patterns between consumers below US dietary recommendations for mature legumes (<37.5 g/day, marginal), below levels showing nutritional and disease-prevention benefits (37.5-87.49 g/day, recommended); and levels demonstrating nutritional and disease prevention benefits (≥87.5 g/day; beneficial). In NHANES, legume consumption remained low in US adults and declined from 2011 to 2014 (mature legumes: 12.8 to 8.3%; dry beans: 10.0 to 6.5%). In BLP, less than 5% consumed legumes daily; approximately one-third did not consume legumes during the last month. Marginal mature-legume consumers ate a limited variety of legumes (dry beans and green legumes on a weekly to monthly basis). Beneficial amount consumers ate mature legumes daily or every other day and included chickpeas, lentils and dry peas to their legume mix. Our data suggest that legume consumption declined in US adults, warranting improved communication about the benefits of regular legume consumption.

Food intake of folate, folic acid and other B vitamins with lung cancer risk in a low-income population in the Southeastern United States.

PURPOSE: We prospectively examined associations of lung cancer risk with food intake of B vitamins involved in one-carbon metabolism and the use of folic acid-containing supplements among a low-income population of black and white adults in the Southeastern US. METHODS: Within the Southern Community Cohort Study, we included 1064 incident lung cancer cases among 68,236 participants aged 40-79 years at study enrollment. Food intake and the use of folic acid-containing supplements were assessed using a validated food frequency questionnaire at study enrollment. Multivariate Cox regression was used to estimate hazards ratios (HRs) and the 95% confidence intervals (CIs). RESULTS: Folate and/or folic acid intake from food were not associated with lung cancer risk; HRs (95% CI) for highest compared with lowest quartile were 1.08 (0.91-1.29) for total dietary folate, 1.00 (0.84-1.19) for food folate, and 1.09 (0.91-1.30) for food folic acid, respectively. Similarly, no associations were observed after stratifying by sex, race and smoking status, except for a positive association with total dietary folate intake among black women (HR 1.46, 95% CI 1.04-2.05 for the highest quartile compared with the lowest quartile, P trend = 0.02). Neither the use of folic acid-containing supplements nor food intake of vitamin B6, vitamin B12 and riboflavin were associated with lung cancer risk. CONCLUSIONS: Our findings do not support a protective effect of folate or folic acid for lung cancer prevention in a low-income population of black and white adults in the Southeastern US. Our finding of a positive association with total dietary folate intake among black women needs to be interpreted with caution and replicated in other studies.

Phytol and its metabolites phytanic and pristanic acids for risk of cancer: current evidence and future directions.

This review summarizes the current evidence on the potential role of phytol, a microbial metabolite of chlorophyl A, and its metabolites, phytanic and pristanic acids, in carcinogenesis. Primary food sources in Western diets are the nut skin for phytol and lipids in dairy, beef and fish for its metabolites. Phytol and its metabolites gained interest as dietary compounds for cancer prevention because, as natural ligands of peroxisome proliferator-activated receptor-α and -γ and retinoid X receptor, phytol and its metabolites have provided some evidence in cell culture studies and limited evidence in animal models of anti-carcinogenic, anti-inflammatory and anti-metabolic-syndrome properties at physiological concentrations. However, there may be a narrow range of efficacy, because phytol and its metabolites at supra-physiological concentrations can cause in vitro cytotoxicity in non-cancer cells and can cause morbidity and mortality in animal models. In human studies, evidence for a role of phytol and its metabolites in cancer prevention is currently limited and inconclusive. In short, phytol and its metabolites are potential dietary compounds for cancer prevention, assuming the challenges in preventing cytotoxicity in non-cancer cells and animal models and understanding phytol metabolism can be mitigated.

Association of Dietary Fiber and Yogurt Consumption With Lung Cancer Risk: A Pooled Analysis.

Importance: Dietary fiber (the main source of prebiotics) and yogurt (a probiotic food) confer various health benefits via modulating the gut microbiota and metabolic pathways. However, their associations with lung cancer risk have not been well investigated. Objective: To evaluate the individual and joint associations of dietary fiber and yogurt consumption with lung cancer risk and to assess the potential effect modification of the associations by lifestyle and other dietary factors. Design, Setting, and Participants: This pooled analysis included 10 prospective cohorts involving 1 445 850 adults from studies that were conducted in the United States, Europe, and Asia. Data analyses were performed between November 2017 and February 2019. Using harmonized individual participant data, hazard ratios and 95% confidence intervals for lung cancer risk associated with dietary fiber and yogurt intakes were estimated for each cohort by Cox regression and pooled using random-effects meta-analysis. Participants who had a history of cancer at enrollment or developed any cancer, died, or were lost to follow-up within 2 years after enrollment were excluded. Exposures: Dietary fiber intake and yogurt consumption measured by validated instruments. Main Outcomes and Measures: Incident lung cancer, subclassified by histologic type (eg, adenocarcinoma, squamous cell carcinoma, and small cell carcinoma). Results: The analytic sample included 627 988 men, with a mean (SD) age of 57.9 (9.0) years, and 817 862 women, with a mean (SD) age of 54.8 (9.7) years. During a median follow-up of 8.6 years, 18 822 incident lung cancer cases were documented. Both fiber and yogurt intakes were inversely associated with lung cancer risk after adjustment for status and pack-years of smoking and other lung cancer risk factors: hazard ratio, 0.83 (95% CI, 0.76-0.91) for the highest vs lowest quintile of fiber intake; and hazard ratio, 0.81 (95% CI, 0.76-0.87) for high vs no yogurt consumption. The fiber or yogurt associations with lung cancer were significant in never smokers and were consistently observed across sex, race/ethnicity, and tumor histologic type. When considered jointly, high yogurt consumption with the highest quintile of fiber intake showed more than 30% reduced risk of lung cancer than nonyogurt consumption with the lowest quintile of fiber intake (hazard ratio, 0.67 [95% CI, 0.61-0.73] in total study populations; hazard ratio, 0.69 [95% CI, 0.54-0.89] in never smokers), suggesting potential synergism. Conclusions and Relevance: Dietary fiber and yogurt consumption was associated with reduced risk of lung cancer after adjusting for known risk factors and among never smokers. Our findings suggest a potential protective role of prebiotics and probiotics against lung carcinogenesis.

Dairy Product Consumption and Prostate Cancer Risk in the United States.

An ongoing controversy exists regarding the effect of dairy products on prostate cancer risk in observational studies. We prospectively investigated the associations between dairy product consumption and prostate cancer risk among men in the United States. After calculating pre-diagnostic intake of individual or subgroups of dairy products using a validated food frequency questionnaire, we estimated hazard ratios (HR) and 95% confidence intervals (CI) for pathologically-verified cases of incident prostate cancer among men, overall, or stratified by severity. Among 49,472 men, 4134 were diagnosed with prostate cancer during an average follow-up period of 11.2 years. The median total dairy intake was 101 g/1000 kcal. Consumption of total, individual, or subgroups of dairy products was not statistically significantly associated with prostate cancer risk overall (HR = 1.05, 95% CI = 0.96-1.15 comparing the highest with lowest quartile) or stratified by severity, except for regular-fat dairy product intake with late-stage prostate cancer risk (HR = 1.37, 95% CI = 1.04-1.82 comparing the highest with lowest quartile) and 2%-fat milk intake with advanced prostate cancer risk (HR = 1.14, 95% CI = 1.02-1.28 comparing the higher than median intake with no intake group). Our findings do not support the previously reported harmful impact of dairy consumption on overall prostate cancer risk among men in the United States.

Trends in Clinical Research Including Asian American, Native Hawaiian, and Pacific Islander Participants Funded by the US National Institutes of Health, 1992 to 2018.

Importance: Advancing the health equity agenda for Asian American, Native Hawaiian, and Pacific Islander (AA/NHPI) individuals has become an intersecting priority for federal agencies. However, the impact of federal investments and legislation to ensure systematic processes and resources to eliminate health disparities in AA/NHPI populations is unclear. Objective: To perform a portfolio review of clinical research funded by the National Institutes of Health (NIH) for AA/NHPI populations and determine the level of NIH investment in serving these populations. Design, Setting, and Participants: Cross-sectional study in which the NIH Research Portfolio Online Reporting Tools Expenditures and Results system was queried for extramural AA/NHPI-focused clinical research projects conducted in the United States from January 1, 1992, to December 31, 2018. Clinical research funded under research project grants, centers, cooperative awards, research career awards, training grants, and fellowships was included, with an advanced text search for AA/NHPI countries and cultures of origin. Project titles and terms were screened for inclusion and project abstracts were reviewed to verify eligibility. Descriptive analyses were completed. Main Outcomes and Measures: Outcomes included NIH funding trends and characteristics of funded projects and organizations. The proportions of AA/NHPI-related funding trends were calculated using 2 denominators, total NIH expenditures and clinical research expenditures. Results: There were 5460 records identified, of which 891 studies were reviewed for eligibility. Of these, 529 clinical research studies focused on AA/NHPI participants composed 0.17% of the total NIH budget over 26 years. Projects studying AA/NHPI individuals in addition to other populations were funded across 17 NIH institutes and centers. The top 5 funders collectively contributed almost 60% of the total funding dollars for AA/NHPI projects and were the National Cancer Institute ($231 584 664), National Institute on Aging ($108 365 124), National Heart, Lung, and Blood Institute ($67 232 910), National Institute on Minority Health and Health Disparities ($62 982 901), and National Institute on Mental Health ($60 072 779). Funding of these projects ($775 536 121) made up 0.17% of the overall NIH expenditures ($451 284 075 000) between 1992 and 2018, and 0.18% ($677 479 468) of the NIH research budget after 2000. Funding for AA/NHPI projects significantly increased over time, but the proportion of the total NIH budget has only increased from 0.12% before 2000 to 0.18% after 2000. Of total funding, 60.8% was awarded to research project grants compared with only 5.1% allocated to research career awards, training grants, and fellowships. Conclusions and Relevance: Increases in research dollars for AA/NHPI clinical research were not associated with increases in the overall NIH research budget, and underrepresentation of AA/NHPI subgroups still remains. Without overt direction from federal entities and dedicated funds for health disparities research, as well as parallel efforts to increase diversity in the biomedical workforce, investments may continue to languish for AA/NHPI populations.

The role of coagulation and platelets in colon cancer-associated thrombosis.

Cancer-associated thrombosis is a common first presenting sign of malignancy and is currently the second leading cause of death in cancer patients after their malignancy. However, the molecular mechanisms underlying cancer-associated thrombosis remain undefined. In this study, we aimed to develop a better understanding of how cancer cells affect the coagulation cascade and platelet activation to induce a prothrombotic phenotype. Our results show that colon cancer cells trigger platelet activation in a manner dependent on cancer cell tissue factor (TF) expression, thrombin generation, activation of the protease-activated receptor 4 (PAR4) on platelets and consequent release of ADP and thromboxane A2. Platelet-colon cancer cell interactions potentiated the release of platelet-derived extracellular vesicles (EVs) rather than cancer cell-derived EVs. Our data show that single colon cancer cells were capable of recruiting and activating platelets and generating fibrin in plasma under shear flow. Finally, in a retrospective analysis of colon cancer patients, we found that the number of venous thromboembolism events was 4.5 times higher in colon cancer patients than in a control population. In conclusion, our data suggest that platelet-cancer cell interactions and perhaps platelet procoagulant EVs may contribute to the prothrombotic phenotype of colon cancer patients. Our work may provide rationale for targeting platelet-cancer cell interactions with PAR4 antagonists together with aspirin and/or ADP receptor antagonists as a potential intervention to limit cancer-associated thrombosis, balancing safety with efficacy.

Plasma selenoprotein P concentration and lung cancer risk: results from a case-control study nested within the Shanghai Men's Health Study.

Selenoprotein P (SELENOP) is a major selenoenzyme in plasma and linked to antioxidant properties and possibly to lung cancer; however, supporting evidence is limited. We investigated the association between pre-diagnostic plasma SELENOP concentration and lung cancer risk in a case-control study of 403 cases and 403 individually matched controls nested within the Shanghai Men's Health Study. SELENOP concentration in pre-diagnostic plasma samples was measured by a sandwich enzyme-linked immunosorbent assay. Cases were diagnosed with lung cancer between 2003 and 2010. Multivariate conditional logistic regression was used to estimate odds ratios (OR) and the corresponding 95% confidence intervals (CI) for studying the association between plasma SELENOP concentration and lung cancer risk. Cases had slightly lower plasma SELENOP concentration than controls (4.3 ± 1.2 versus 4.4 ± 1.1 mg/l, P difference = 0.09). However, the multivariate analysis showed no association between plasma SELENOP concentration and lung cancer risk among all participants (OR = 1.08, 95% CI = 0.54-2.14 for quartile 4 versus quartile 1), or by smoking status or tumor aggressiveness. In contrast, although the number of cases was limited, plasma SELENOP concentration was positively associated with lung adenocarcinoma risk (OR = 5.38, 95% CI = 1.89-15.35 for tertile 3 versus tertile 1), but not with squamous cell lung carcinoma (OR = 1.69, 95% CI = 0.43-6.70). Our study of adult men living in selenium non-deficient areas in China provides little support for the inverse association between pre-diagnostic plasma SELENOP concentration and lung cancer risk. Our finding of a positive association with risk of lung adenocarcinoma needs to be interpreted with caution.