Development of broad-spectrum antiviral therapies is critical for outbreak and pandemic preparedness against emerging and reemerging viruses. Viruses inducing hemorrhagic fevers cause high morbidity and mortality in humans and are associated with several recent international outbreaks, but approved therapies for treating most of these pathogens are lacking. Here, we show that 4'-fluorouridine (4'-FlU; EIDD-2749), an orally available ribonucleoside analog, has antiviral activity against multiple hemorrhagic fever viruses in cell culture, including Nipah virus, Crimean-Congo hemorrhagic fever virus, orthohantaviruses, and arenaviruses. We performed preclinical in vivo evaluation of oral 4'-FlU against two arenaviruses, Old World Lassa virus (LASV) and New World Junín virus (JUNV), in guinea pig models of lethal disease. 4'-FlU demonstrated both advantageous pharmacokinetic characteristics and high efficacy in both of these lethal disease guinea pig models. Additional experiments supported protection of the infected animals even when 4'-FlU delivery was reduced to a low dose of 0.5 milligram per kilogram. To demonstrate clinical utility, 4'-FlU treatment was evaluated when initiated late in the course of infection (12 or 9 days after infection for LASV and JUNV, respectively). Delayed treatment resulted in rapid resolution of clinical signs, demonstrating an extended window for therapeutic intervention. These data support the use of 4'-FlU as a potent and efficacious treatment against highly pathogenic arenaviruses of public health concern with a virus inhibition profile suggesting broad-spectrum utility as an orally available antiviral drug against a wide variety of viral pathogens.

Introduction: Internal standards correct for measurement variation due to sample loss. Isotope labeled analytes are ideal internal standards for the measurement of fatty acids in human plasma but are not always readily available. For this reason, quantification of multiple analytes at once is most often done using only a single or few internal standards. The magnitude of the impact this has on method accuracy and precision is not well studied for gas chromatography-mass spectrometry systems. Objective: This study aims to estimate bias and changes in uncertainty associated with using alternative fatty acid isotopologue internal standards for the estimation of similar or dissimilar long chain fatty acids. Method: Using a previously reported method for the quantification of 27 fatty acids in human plasma using 18 internal standards we obtained estimates of bias and uncertainty at up to three levels of fatty acid concentration. Results: With some notable exceptions, method accuracy remained relatively stable when using an alternative internal standard (Median Relative Absolute Percent Bias: 1.76%, Median Spike-Recovery Absolute Percent Bias: 8.82%), with larger changes in method precision (Median Increase in Variance: 141%). Additionally, the degree of difference between analyte and internal standard structure was related to the magnitude of bias and uncertainty of the measurement. Conclusion: The data presented here show that the choice of internal standard used to estimate fatty acid concentration can affect the accuracy and reliability of measurement results and, therefore, needs to be assessed carefully when developing analytical methods for the measurement of fatty acid profiles. Disclaimer: The findings and conclusions in this report are those of the author(s) and do not necessarily represent the official position of the Centers for Disease Control and Prevention/the Agency for Toxic Substances and Disease Registry. Use of trade names is for identification only and does not imply endorsement by the Centers for Disease Control and Prevention, the Public Health Service, and the US Department of Health and Human Services. © 2024

Few methods have been used to characterize repeatedly measured biomarkers of chemical mixtures. We applied latent profile analysis (LPA) to serum concentrations of four perfluoroalkyl and polyfluoroalkyl substances (PFAS) at four timepoints from gestation to age 12 years. We evaluated the relations between profiles and z-scores of height, body mass index, fat mass index, and lean body mass index at age 12 years (n = 218). We compared LPA findings with an alternative approach for cumulative PFAS mixtures using g-computation to estimate the effect of simultaneously increasing the area under the curve (AUC) for all PFAS. We identified two profiles: a higher (35% of sample) and lower PFAS profile (relative to each other), based on their average PFAS concentrations at all timepoints. The higher PFAS profile had generally lower z-scores for all outcomes, with somewhat larger effects for males, though all CIs crossed the null. For example, the higher PFAS profile was associated with a -0.50 (95% CI: -1.07, 0.08) lower BMI z-score among males but not females (0.04; 95% CI: -0.45, 0.54). We observed similar patterns with AUCs. We found that higher childhood PFAS profile and higher cumulative PFAS mixtures may be associated with altered growth in early adolescence.

BACKGROUND: Early-life phthalate exposures may disrupt metabolic processes; however few prospective studies have assessed whether these associations extend to cardiometabolic outcomes during adolescence. METHODS: Among 183 mother-adolescent pairs in a prospective cohort study that enrolled pregnant women in Cincinnati, OH (2003-2006), we quantified nine phthalate metabolites in spot urine samples collected twice from mothers during pregnancy and up to seven times from children. At age 12 years, we assessed triglycerides, high-density (HDL) and low-density (LDL) lipoprotein cholesterol, insulin, and glucose from fasting serum samples and calculated homeostatic model assessment of insulin resistance (HOMA-IR). Using multiple informant models, we estimated covariate-adjusted associations between urinary phthalate concentrations at each time period and cardiometabolic biomarkers at age 12 years, including modification by child sex. RESULTS: Although most associations were weak or null, monoethyl phthalate (MEP), mono-n-butyl phthalate (MnBP), mono-isobutyl phthalate (MiBP), and monobenzyl phthalate (MBzP) concentrations were generally associated with lower LDL at age 12 years. A 10-fold increase in 4- and 12-year MEP was associated with -15.3mg/dL (95% CI: 27.5, -3.13mg/dL) and -11.8mg/dL (-22.0, -1.51mg/dL) lower LDL, respectively. Discrepant associations were observed in females versus males: a 10-fold increase in 3-year MEP concentrations was associated with 12.0mg/dL (95% CI: 7.11, 31.1mg/dL) higher LDL levels in males and -30.4mg/dL (95% CI: 50.9, -9.8mg/dL) lower LDL levels in females. Some urinary phthalate concentrations were cross-sectionally associated with HOMA-IR. CONCLUSIONS: Early-life phthalate biomarker concentrations may be inversely associated with LDL during early adolescence in an exposure-period and sex-dependent manner.

BACKGROUND: Early life environmental exposures may affect bone mass accrual in childhood, but only one study has assessed the role of environmental phenols on child bone health. METHODS: We used data from 223 mother-child dyads enrolled in the Health Outcomes and Measures of the Environment (HOME) Study (Cincinnati, OH; 2003-2006). We quantified benzophenone-3, bisphenol A (BPA), 2,5-dichlorophenol, and triclosan in maternal urine collected at 16- and 26-weeks gestation and calculated the average of creatinine-adjusted concentrations. We performed dual x-ray absorptiometry at age 12 years and calculated Z-scores for whole body (less head), total hip, femoral neck, and 1/3rd distal radius bone mineral content (BMC) and areal bone mineral density (aBMD) as well as ultra-distal radius aBMD and spine BMC and bone mineral apparent density (BMAD). We estimated covariate-adjusted associations per doubling of maternal urinary environmental phenol concentrations in linear regression models. We also examined effect measure modification by child's sex and estimated associations of the environmental phenol mixture with BMC and aBMD using quantile g-computation. RESULTS: We observed generally null associations for all analytes and bone measures. Yet, in adjusted models, higher urinary 2,5-dichlorophenol concentrations were associated with higher 1/3rd distal radius BMC (: 0.09; 95% CI: 0.02, 0.17) and aBMD (: 0.09; 95% CI: 0.02, 0.17) Z-scores in the overall sample. In sex-stratified analyses, the magnitude of the BMC association was positive for females (: 0.16; 95% CI: 0.06, 0.26) and null for males (: 0.02; 95% CI: 0.08, 0.13). The environmental phenol mixture was associated with greater 1/3rd distal radius BMC and aBMD Z-scores in both sexes, which was mostly driven by benzophenone-3 in males and 2,5-dichlorophenol in females. CONCLUSION: In this prospective cohort study, we observed generally null associations for environmental phenols with BMC and aBMD at age 12 years. While there was a positive association of 2,5-dichlorophenol concentrations during fetal development with distal radius BMC and aBMD at age 12 years, future studies utilizing methods capable of differentiating cortical and trabecular bone are needed to elucidate potential mechanisms and implications for bone strength and microarchitecture.

PURPOSE: We conducted a 12-month pilot study of 2 complementary strategies for improving rural cancer survivorship outcomes: (1) Project ECHO, a telementoring model to increase knowledge and skills about cancer survivorship among multidisciplinary health care provider teams in rural areas and (2) patient navigation (PN) services to connect rural cancer survivors with resources for enhancing health and wellness. METHODS: We recruited 4 CDC-funded National Comprehensive Cancer Control Program sites to implement Project ECHO and PN interventions for a defined rural population in each of their jurisdictions. Sites received ongoing technical assistance and a stipend to support implementation. We conducted a mixed-methods evaluation consisting of quantitative performance monitoring data and qualitative interviews with site staff to assess implementation. FINDINGS: Site teams delivered 21 cancer survivorship ECHO sessions to rural providers resulting in 329 participant encounters. Almost all (93%) ECHO participants reported enhanced knowledge of cancer survivorship issues, and 80% reported intent to apply learnings to their practices. Site teams engaged 16 patient navigators who navigated 164 cancer survivors during the study period. Successful implementation required strong partnerships, clear avenues for recruitment of rural providers and cancer survivors, and activities tailored to local needs. Fostering ongoing relationships among sites through community of practice calls also enhanced implementation. CONCLUSIONS: Sites successfully implemented a novel approach for enhancing care for cancer survivors in rural communities. Pairing Project ECHO to address structural barriers and PN to address individual factors affecting survivorship may help bridge the health equity gap experienced by cancer survivors in rural communities.

BACKGROUND: Early life phthalate exposures may disrupt metabolism but results from human studies are inconsistent and few have examined body composition during adolescence. We investigated associations of gestational and childhood urinary phthalate biomarker concentrations with body composition at age 12 years. METHODS: We used data from 206 mother-child pairs in a prospective pregnancy and birth cohort enrolled in Cincinnati, OH from 2003 to 2006. We measured nine phthalate metabolites in spot urine samples collected twice from mothers during pregnancy and up to seven times from children at 1, 2, 3, 4, 5, 8, and 12 years. At age 12 years, we assessed fat and lean mass of the whole body and android and gynoid subregions, and visceral fat area with dual x-ray absorptiometry, and calculated android to gynoid %fat ratio and age- and sex-standardized fat and lean mass index z-scores. Using a multiple informant model, we estimated covariate-adjusted associations between urinary phthalate biomarker concentrations at each time period and outcomes at age 12 years. We assessed effect measure modification by child sex using stratified models. RESULTS: Generally, urinary mono-benzyl phthalate (MBzP) concentrations were modestly associated with lower fat and lean mass. Each 10-fold increase in urinary MBzP concentrations during gestation and at ages 5 and 8 years was associated with a -0.34 (95%CI: -0.72, 0.05), -0.44 (95% CI: -0.83, -0.05), and -0.35 (95% CI: -0.71, 0.00) z-score difference in lean body mass index, respectively. Urinary monoethyl phthalate, mono-(3-carboxypropyl) phthalate, and summed di(2-ethylhexyl) phthalate metabolites were associated with greater lean mass at some exposure periods. Slightly weaker but similar patterns of association were found with other body composition measures; associations did not differ by child sex. CONCLUSION: While most associations were weak, exposure to certain phthalates during gestation and childhood may be associated with adolescent body composition, particularly lean mass.

Objectives: Intake of trans fatty acids (TFA) increases the risk of cardiovascular disease. Assessment of TFA exposure in the population is key for determining TFA burden and monitoring change over time. One approach for TFA monitoring is measurement of TFA levels in plasma. Understanding costs associated with this approach can facilitate program planning, implementation and scale-up. This report provides an assessment of costs associated with a pilot program to measure plasma TFA levels in Thailand. Study design: Cost analysis in a laboratory facility in Thailand. Methods: We defined three broad cost modules: laboratory, personnel, and facility costs, which were further classified into sub-components and into fixed and variable categories. Costs were estimated based on the number of processed plasma samples (100–2700 in increments of 50) per year over a certain number of years (1–5), in both USD and Thai Baht. Total cost and average costs per sample were estimated across a range of samples processed. Results: The average cost per sample of analyzing 900 samples annually over 5 years was estimated at USD186. Laboratory, personnel, and facility costs constitute 67%, 23%, and 10% of costs, respectively. The breakdown across fixed costs, such as laboratory instruments and personnel, and variable costs, such as chemical supplies, was 60% and 40%, respectively. Average costs decline as more samples are processed: the cost per sample for analyzing 100, 500, 1500, and 2500 samples per year over 5 years is USD1351, USD301, USD195; and USD177, respectively. Conclusions: Laboratory analysis of plasma TFA levels has high potential for economies of scale, encouraging a long-term approach to TFA monitoring initiatives, particularly in countries that already maintain national biometric repositories. © 2021 The Authors

BACKGROUND: The developing fetus may be particularly susceptibility to environmental osteotoxicants, but studies of pregnancy phthalate exposures and childhood bone health are scarce. OBJECTIVES: To examine relations of pregnancy phthalate exposure biomarkers with early adolescent bone mineral density (BMD) and bone mineral content (BMC) in a prospective birth cohort. METHODS: We used data from 223 pregnant mothers and their children enrolled in a Cincinnati, OH area cohort from 2003 to 2006. We quantified monoethyl phthalate (MEP), monoisobutyl phthalate, monobutyl phthalate, monobenzyl phthalate, mono-(3-carboxypropyl) phthalate (MCPP), and four metabolites of di-2-ethylhexyl phthalate in maternal urine collected at 16 and 26 weeks gestation, and calculated the average of creatinine-standardized concentrations. Using dual x-ray absorptiometry measures at age 12 years, we calculated BMD and BMC Z-scores for six skeletal sites. In overall and sex-stratified models, we estimated covariate-adjusted associations per 2-fold increase in phthalate biomarker concentrations using linear regression, and estimated joint effects of the phthalate biomarkers mixture using Bayesian kernel machine regression (BKMR) and quantile g-computation. RESULTS: In single phthalate models, several biomarkers were positively associated with BMC and BMD. For example, each doubling of MEP and MCPP, 1/3rd distal radius BMD Z-score increased by 0.09 (95% CI: 0.01, 0.17) and 0.16 (95% CI: 0.01, 0.31), respectively. For phthalate mixtures, associations were generally U-shaped among males and positive-linear among females, using both statistical methods. Mixture associations were strongest with forearm sites: in BKMR models, increasing all biomarkers from the 50th to 90th percentile was associated with a 0.64 (95% CI: 0.01, 1.28) greater 1/3rd distal radius BMD Z-score in males, and a 0.49 (95% CI: -0.13, 1.10) greater ultradistal radius BMD Z-score in females. DISCUSSION: In this study, phthalate exposures during gestation were associated with increased BMD Z-scores in early adolescence, though further research is needed to determine implications for long-term skeletal health.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) may impair bone accrual and strength via endocrine disruption and nuclear receptor agonism, but human studies are primarily of adults or cross-sectional. OBJECTIVES: We assessed associations of individual PFAS and their mixture during pregnancy with child bone mineral content (BMC) and areal bone mineral density (aBMD) at age 12 y. METHODS: Among 206 mother-child pairs enrolled in a prospective cohort (2003-2006), we quantified perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorohexane sulfonic acid (PFHxS), and perfluorooctane sulfonic acid (PFOS) in maternal serum collected during gestation or delivery. When children were age 12 y, we performed dual energy X-ray absorptiometry and calculated BMC, aBMD, and bone mineral apparent density (BMAD) z-scores for six skeletal sites. We estimated covariate-adjusted z-score differences per doubling of individual PFAS using linear regression and assessed the PFAS mixture using quantile g-computation and Bayesian kernel machine regression. We explored whether associations were modified by child's sex or mediated by whole-body lean mass. RESULTS: In covariate-adjusted models, we found that higher maternal serum concentrations of PFOA, PFNA, and the PFAS mixture were associated with lower total hip and forearm (one-third distal radius) BMC z-scores in children. Differences in forearm BMC z-scores were - 0.17 [95% confidence interval (CI): - 0.35, 0.01] and - 0.24 (95% CI: - 0.44, - 0.05) per doubling of PFOA and PFNA, respectively, and - 0.18 (95% CI: - 0.34, - 0.02) per quartile increase in the PFAS mixture. Child's sex modified PFOA associations for some skeletal sites; for example, differences in spine BMAD z-score per doubling were - 0.31 (95% CI: - 0.58, - 0.03) among males and 0.07 (95% CI: - 0.16, 0.30) among females (modification p = 0.04). Except for PFNA among females, these associations were not mediated by whole-body lean mass. DISCUSSION: Maternal PFAS concentrations during pregnancy may be associated with lower bone mineral accrual and strength in early adolescence. https://doi.org/10.1289/EHP9424.

BACKGROUND: Intake of trans fatty acids (TFAs) increases LDL cholesterol, decreases HDL cholesterol, and increases the risk of heart disease morbidity and mortality. Many food products potentially contain industrially produced or ruminant TFAs. However, little is known about the dietary sources of plasma TFA concentrations. OBJECTIVE: The objective of this study was to examine associations between foods consumed and plasma TFA concentrations using 24-h dietary recall data and plasma TFA measures among adults aged ≥20 y who participated in the NHANES 2009-2010 in the United States. METHODS: Over 4400 food products in the dietary interview data were categorized into 32 food and beverage groups/subgroups. Four major plasma TFAs (palmitelaidic acid, elaidic acid, vaccenic acid, linolelaidic acid) and the sum of the 4 TFAs (sumTFAs) were analyzed using GC-MS. Multivariable linear regression analyses were conducted to identify associations of plasma TFAs with all 32 food and beverage groups/subgroups, controlling for the potential confounding effects of 11 demographic, socioeconomic, behavioral, lifestyle, and health-related variables. RESULTS: Consumption of the following food groups/subgroups was significantly associated with elevated plasma TFA concentrations: cream substitutes (P < 0.001 for palmitelaidic acid, elaidic acid, vaccenic acid, and sumTFAs); cakes, cookies, pastries, and pies (P < 0.001 for elaidic acid, vaccenic acid, and sumTFAs; P < 0.05 for linolelaidic acid); milk and milk desserts (P < 0.01 for palmitelaidic acid and vaccenic acid; P < 0.05 for linolelaidic acid and sumTFAs); beef/veal, lamb/goat, and venison/deer (P < 0.01 for vaccenic acid; P < 0.05 for sumTFAs); and butters (P < 0.001 for palmitelaidic acid and vaccenic acid; P < 0.05 for sumTFAs). CONCLUSIONS: The findings suggest that the above 5 food groups/subgroups could be the main dietary sources of plasma TFAs among adults in the United States in 2009-2010.

Introduction: Asian immigrants to the U.S. smoke at higher rates than U.S.-born Asians. However, few programs exist to help these immigrants quit and little is known about their real-world effectiveness. The Centers for Disease Control and Prevention funded the Asian Smokers' Quitline to serve Chinese, Korean, and Vietnamese immigrants nationwide. This study examines service utilization and outcomes from the first 7 years of the program. Method(s): From August 2012 to July 2019, the Asian Smokers' Quitline enrolled 14,073 Chinese-, Korean-, and Vietnamese-speaking smokers. Service utilization rates and cessation outcomes were compared with those of an earlier trial (conducted 2004-2008) that demonstrated the efficacy of an Asian-language telephone counseling protocol. Data were analyzed in 2019. Result(s): Asian Smokers' Quitline participants came from all 50 states and the District of Columbia. The main referral sources were Asian-language newspapers (37.2%), family and friends (16.4%), healthcare providers (11.9%), and radio (11.9%). Overall, 37.6% were uninsured, 38.8% had chronic health conditions, and 15.4% had mental health conditions. Compared with participants in the earlier trial, Quitline participants received 1 fewer counseling session (3.8 vs 4.9, p<0.001) but were more likely to use pharmacotherapy (73.6% vs 20.9%, p<0.001). More than 90% were satisfied with the services they received. Six-month prolonged abstinence rates were higher in the Quitline than in the trial (complete case analysis: 28.6% vs 20.0%, p<0.001; intention-to-treat analysis: 20.5% vs 16.4%, p=0.005). Conclusion(s): The Asian Smokers' Quitline was utilized by >14,000 Asian-language-speaking smokers across the U.S. in its first 7 years. This quitline could serve as a model for delivering other behavioral services to geographically dispersed linguistic minority populations.

INTRODUCTION: A gradual reduction of cigarette nicotine content to nonaddictive levels has been proposed as an endgame strategy to accelerate declines in combustible tobacco smoking. We assessed manufacturer-reported nicotine yield in cigarettes sold in the United States from 2013 to 2016. METHODS: We merged machine-measured nicotine yield in cigarette smoke and pack characteristics obtained from reports filed by tobacco manufacturers with the Federal Trade Commission for 2013-2016 with monthly Nielsen data on US cigarette sales. Manufacturer-reported, sales-weighted, average annual nicotine yield was assessed, as were nicotine yield sales trends by quartile: markedly low (0.10-0.60 mg/stick), low (0.61-0.80 mg/stick), moderate (0.81-0.90 mg/stick), and high (0.91-3.00 mg/stick). Trends in overall, menthol, and nonmenthol pack sales, by nicotine yield quartiles over the study period and by year, were determined by using Joinpoint regression. RESULTS: During 2013-2016, average annual sales-weighted nicotine yield for all cigarettes increased from 0.903 mg/stick (95% CI, 0.882-0.925) in 2013 to 0.938 mg/stick (95% CI, 0.915-0.962) in 2016 (P < .05). For menthol cigarettes, yield increased from 0.943 mg/stick in 2013 (95% CI, 0.909-0.977) to 1.037 mg/stick in 2016 (95% CI, 0.993-1.081), increasing 0.2% each month (P < .05). Most pack sales occurred among high (41.5%) and low (30.7%) nicotine yield quartiles. Cigarette sales for the markedly low quartile decreased by an average of 0.4% each month during 2013-2016 (P < .05). CONCLUSION: During 2013-2016, manufacturer-reported, sales-weighted nicotine yield in cigarettes increased, most notably for menthol cigarettes. Continued monitoring of nicotine yield and content in cigarettes can inform tobacco control strategies.

Non-communicable diseases (NCDs) are the leading causes of death in the United States Affiliated Pacific Islands (USAPIs); US Centers for Disease Control and Prevention funds programs for prevention and control of diabetes, tobacco use, and related chronic disease conditions. To build USAPI programs' capacity in evaluation and surveillance, we held in-person and virtual trainings on evaluation planning and logic models that were tailored with traditional canoe-building themes to be relatable and memorable. Evaluation results suggest the efforts were effective at translating concepts. Additional tools and technical assistance reinforced concepts and resulted in quality evaluation plans. Culturally tailored evaluation tools can be useful and should be developed with population representatives.

OBJECTIVES: To estimate the impact of the 2006 policy restricting use of trans fatty acids (TFAs) in New York City restaurants on change in serum TFA concentrations in New York City adults. METHODS: Two cross-sectional population-based New York City Health and Nutrition Examination Surveys conducted in 2004 (n = 212) and 2013-2014 (n = 247) provided estimates of serum TFA exposure and average frequency of weekly restaurant meals. We estimated the geometric mean of the sum of serum TFAs by year and restaurant meal frequency by using linear regression. RESULTS: Among those who ate less than 1 restaurant meal per week, geometric mean of the sum of serum TFAs declined 51.1% (95% confidence interval [CI] = 42.7, 58.3)-from 44.6 (95% CI = 39.7, 50.1) to 21.8 (95% CI = 19.3, 24.5) micromoles per liter. The decline in the geometric mean was greater (P for interaction = .04) among those who ate 4 or more restaurant meals per week: 61.6% (95% CI = 55.8, 66.7) or from 54.6 (95% CI = 49.3, 60.5) to 21.0 (95% CI = 18.9, 23.3) micromoles per liter. CONCLUSIONS: New York City adult serum TFA concentrations declined between 2004 and 2014. The indication of greater decline in serum TFAs among those eating restaurant meals more frequently suggests that the municipal restriction on TFA use was effective in reducing TFA exposure. Public Health Implications. Local policies focused on restaurants can promote nutritional improvements. (Am J Public Health. Published online ahead of print February 21, 2019: e1-e3. doi:10.2105/AJPH.2018.304930).

INTRODUCTION: The use of flavored tobacco products, including electronic cigarettes (e-cigarettes), is common in the United States, and flavored products are particularly appealing to young people. The objective of this study was to describe national and state trends in flavored and menthol e-cigarette unit sales. METHODS: We examined data on 4 types of e-cigarette products (rechargeables, disposables, prefilled cartridges, and e-liquid refills). We used Universal Product Code retail scanner data from 2 sources: 1) convenience stores and 2) all other outlets combined, including supermarkets, drug stores, mass merchandisers (including Walmart), dollar stores, club stores, and US Department of Defense commissaries. We aggregated data in 4-week periods for the 48 contiguous states and the District of Columbia for the 5-year period from 2012 through 2016. Data from vape shops and internet sales were not available. We used Joinpoint regression to assess trends. RESULTS: From 2012 through 2016, flavored e-cigarette sales as a percentage of all e-cigarette sales increased nationally (from 2.4% to 19.8%) and in all but 4 states (North Dakota, South Dakota, Utah, and Vermont). Nationally, flavored disposable and prefilled cartridge sales increased. Menthol e-cigarette sales were stable nationally at 35% to 40%, while the percentage of menthol disposable, prefilled cartridge, and e-liquid refill sales decreased. By state, menthol e-cigarette sales increased in 2 states (Idaho and Nebraska) and decreased in 7 states. During 2015-2016, the percentage of flavored sales decreased in one state (Rhode Island) and increased in 29 states. CONCLUSION: These findings demonstrate that sales of flavored e-cigarette products have increased dramatically since 2012, with variations by product type and state. Continued monitoring of sales trends at all retail outlets can inform federal, state, and local efforts to address flavored tobacco product use, including e-cigarettes, in the United States.

INTRODUCTION: Few studies have explored patterns of electronic cigarette (e-cigarette) sales and prices by product type over time. We used US retail scanner data to assess national and state-specific trends in e-cigarette unit sales and prices for 4 product types sold from 2012 through 2016. METHODS: Using retail scanner data from the 48 contiguous states and Washington, DC, for convenience stores; supermarkets; mass merchandisers; drug, dollar, and club stores; and military commissaries, we assessed data on monthly unit sales and inflation-adjusted prices by 4 products (rechargeables, disposables, prefilled cartridges, and e-liquids) sold during the 5-year study period. We evaluated national and state trends by using Joinpoint regression (P < .05). RESULTS: From 2012 through 2016, average national monthly unit sales significantly increased for all products, while average monthly prices of rechargeables, disposables, and prefilled cartridges significantly decreased. In 2016, prefilled cartridges had the highest average sales (766 units per 100,000 people) and the lowest average price ($14.36 per unit). By state, average monthly sales significantly increased for at least 1 of 4 e-cigarette products in all 48 states and Washington, DC. However, during the same period, average monthly prices significantly decreased in 39 states for rechargeables, in 31 states for disposables, in 20 states for prefilled cartridges, and in 8 states for e-liquids. CONCLUSION: Overall, US e-cigarette unit sales generally increased as product prices decreased. These findings demonstrate the rapidly evolving landscape of US e-cigarette retail marketplace. Ongoing surveillance of e-cigarette unit sales and price is critical for informing and evaluating evidence-based tobacco control strategies.

INTRODUCTION: Cigar sales have increased in the USA in recent years. A growing proportion of cigar sales are of flavoured varieties, many bearing ambiguous or 'concept' flavour descriptions (eg, Jazz). This study assessed US cigar sales by flavour category (ie, concept flavoured, characterising flavoured and tobacco), at national, regional and state levels. METHODS: Sales of cigarillos, large cigars and little cigars from chain, franchise and convenience stores, mass merchandisers, supermarkets, drug, dollar and club stores, and military commissaries during 2012-2016 were acquired from the Nielsen Company. US national-level and state-level sales, including District of Columbia, were analysed by flavour category. Flavour descriptors were classified as 'tobacco', 'characterising' or 'concept', based on Universal Product Code (UPC)-linked characteristics and brand website and consumer review descriptions. RESULTS: Cigar sales increased by 29% during 2012-2016, driven by a 78% increase in cigarillo sales. The proportion of concept-flavoured sales increased from 9% to 15%, while the proportion of sales decreased for tobacco (50% to 49%) and characterising flavours (eg, cherry) (41% to 36%). Cigarillos had the greatest increase in unique concept flavour descriptions (17 to 46 unique UPCs), with most sales occurring among Sweet, Jazz and Green Sweets concept flavours. By US region, total and concept-flavoured cigarillo sales were highest in the South. CONCLUSIONS: Flavoured cigars are increasingly labelled with concept flavours, including in areas with flavoured tobacco sales restrictions. Cigarillos are driving recent increases in US cigar and concept-flavoured cigar sales. It is important to consider concept flavours when addressing flavoured tobacco product sales and use.

The outcome indicator framework helps tobacco prevention and control programs (TCPs) plan and implement theory-driven evaluations of their efforts to reduce and prevent tobacco use. Tobacco use is the single-most preventable cause of morbidity and mortality in the United States. The implementation of public health best practices by comprehensive state TCPs has been shown to prevent the initiation of tobacco use, reduce tobacco use prevalence, and decrease tobacco-related health care expenditures. Achieving and sustaining program goals require TCPs to evaluate the effectiveness and impact of their programs. To guide evaluation efforts by TCPs, the Centers for Disease Control and Prevention's Office on Smoking and Health developed an outcome indicator framework that includes a high-level logic model and evidence-based outcome indicators for each tobacco prevention and control goal area. In this article, we describe how TCPs and other community organizations can use the outcome indicator framework in their evaluation efforts. We also discuss how the framework is used at the national level to unify tobacco prevention and control efforts across varying state contexts, identify promising practices, and expand the public health evidence base.

Trans-fatty acids (TFA) are geometric isomers of naturally occurring cis-fatty acids. High dietary TFA intake has been associated with risk factors for cardiovascular disease. However, little is known about TFA levels in humans. To address this data need, we developed and validated a new isotope dilution-gas chromatography-negative chemical ionization-mass spectrometry (ID-GC-NCI-MS) method for quantitation of 27 fatty acids (FA) including 4 major TFA in human plasma, serum, and red blood cells (RBC) from 66 donors. Quantitation was performed with 18 isotope labeled internal standards and results are presented in muM and % of total FA. This method has high sensitivity and specificity due to use of pentafluorobenzyl-bromide derivatization combined with NCI-MS and a 200m column to optimize positional and geometric FA isomer separation. The four major TFA, palmitelaidic acid, elaidic acid, trans-vaccenic acid, and linoelaidic acid, were detected in all samples, with median total TFA concentrations of 17.7muM in plasma, 19.6muM in serum, and 21.5muM in RBC. The % of total FA for the TFA was 0.20% in plasma, 0.20% in serum, and 0.30% in RBC. Patterns for % FA are similar to those reported in other studies. We developed a highly specific, ID-GC-NCI-MS method to quantitate TFA and other FA in humans.

Introduction: Tobacco manufacturers continue to implement a range of pricing strategies to increase the affordability and consumption of tobacco products. To demonstrate the extent of retail- and brand-level price discounts at the point of sale, this study assessed national sales trends in price-discounted cigarettes, large cigars, little cigars, and cigarillos. Methods: Retail scanner data for tobacco product sales were obtained for convenience stores (C-store) and all-other-outlets-combined (AOC) from September 25, 2011, to January 9, 2016. The proportion of price-discounted sales, average nondiscounted unit price, and average discounted unit price were examined by product category and brand. JoinPoint regression was used to assess average monthly percentage change. Results: Overall, price-discounted sales accounted for 11.3% of cigarette, 3.4% of large cigar, 4.1% of little cigar, and 3.9% of cigarillo sales. The average difference between nondiscounted and discounted prices was 25.5% (C-store) and 36.7% (AOC) for cigarettes; 11.0% (C-store) and 11.2% (AOC) for large cigars; 19.2% (C-store) and 9.6% (AOC) for little cigars; and 5.3% (C-store) and 14.7% (AOC) for cigarillos. Furthermore, price-discounted sales of top-selling tobacco brands comprised up to 36% of cigarette, 7.4% of large cigar, 7.7% of little cigar, and 4.2% of cigarillo unit sales. Conclusions: These findings highlight the use of price discounts by tobacco manufacturers to reduce the cost of cigarettes, large cigars, little cigars, and cigarillos to consumers. These sales patterns underscore the importance of sustained efforts to implement evidence-based strategies to increase prices and reduce availability and consumption of combustible tobacco in the United States. Implications: This study highlights the prevalence and provides a baseline of price-discounted cigarettes, large cigars, little cigars, and cigarillos. Surveillance of tobacco sales data, including state-level trends and additional product types, is critical for informing approaches to reduce tobacco consumption. These approaches include countering tobacco product price-discounting practices and raising and maintaining a high sales price for all tobacco products. The implementation of evidence-based population-level interventions, together with local, state, and federal regulation of tobacco products, could prevent tobacco initiation, increase tobacco cessation, and reduce overall tobacco use among US youth and adults.

Introduction: Flavors can mask the harshness of tobacco and make it appealing to young people. This study assessed flavored and menthol tobacco product sales at the national and state levels. Methods: Universal Product Code (UPC) tobacco sales data collected by Nielsen were combined for convenience stores and all-outlets-combined during October 22, 2011-January 9, 2016. Products were characterized as flavored, menthol, or non-flavored/non-menthol. Total unit sales, and the proportion of flavored and menthol unit sales, were assessed nationally and by state for seven tobacco products. Joinpoint Regression was used to assess trends in average monthly percentage change. Results: Nationally, the proportion of flavored and menthol sales in 2015 was as follows: cigarettes (32.5% menthol), large cigars (26.1% flavored), cigarillos (47.5% flavored, 0.2% menthol), little cigars (21.8% flavored, 19.4% menthol), chewing tobacco (1.4% flavored, 0.7% menthol), moist snuff (3.0% flavored, 57.0% menthol), and snus (88.5% menthol). From 2011-2015, sales increased for flavored cigarillos and chewing tobacco, as well as for menthol cigarettes, little cigars, moist snuff and snus. Sales decreased for flavored large cigars, moist snuff and snus, and for menthol chewing tobacco. State-level variations were observed by product; for example, flavored little cigar sales ranged from 4.4% (Maine) to 69.3% (Utah) and flavored cigarillo sales ranged from 26.6% (Maine) to 63.0% (Maryland). Conclusions: Menthol and flavored sales have increased since 2011, particularly for the products with the highest number of units sold, and significant state variation exists. Efforts to restrict flavored tobacco product sales could reduce overall U.S. tobacco consumption. Implications: Flavors in tobacco products can mask the harshness of tobacco and make these products more appealing to young people. This is the first study to assess national and state-level trends in flavored and menthol tobacco product sales. These findings underscore the importance of population-based interventions to address flavored tobacco product use at the national, state, and local levels. Additionally, further monitoring of flavored and menthol tobacco product sales can inform potential future regulatory efforts at the national, state, and local levels.

Background: The consumption of trans fatty acids (TFAs) is associated with an increased risk of cardiovascular disease, and reducing their consumption is a major public health objective. Food intake studies have provided estimates for TFA concentrations in the US population; however, there is a need for data on TFA blood concentrations in the population.Objective: The objective of this study was to determine plasma TFA concentrations in a nationally representative group of fasted adults in the US population in NHANES samples from 1999-2000 and 2009-2010.Design: Four major TFAs [palmitelaidic acid (C16:1n-7t), trans vaccenic acid (C18:1n-7t), elaidic acid (C18:1n-9t), and linoelaidic acid (C18:2n-6t,9t)] were measured in plasma in 1613 subjects from NHANES 1999-2000 and 2462 subjects from NHANES 2009-2010 by gas chromatography-mass spectrometry. Geometric means and distribution percentiles were calculated for each TFA and their sum by age, sex, and race/ethnicity (non-Hispanic white, non-Hispanic black, Mexican American), and covariate-adjusted geometric means were computed by using a model that included these demographic and other dietary factors, as well as survey year and any significant interaction terms.Results: These nationally representative data for the adult US population show that TFA concentrations were 54% lower in NHANES 2009-2010 than in NHANES 1999-2000. Covariate-adjusted geometric means for the sum of the 4 TFAs were 81.4 mumol/L (95% CI: 77.3, 85.6 mumol/L) and 37.8 mumol/L (95% CI: 36.4, 39.4 mumol/L) in NHANES 1999-2000 and 2009-2010, respectively. Even with the large decline in TFA concentrations, differences between demographic subgroups were comparable in the 2 surveys.Conclusion: The results indicate an overall reduction in TFA concentrations in the US population and provide a valuable baseline to evaluate the impact of the recent regulation categorizing TFAs as food additives.

Multiunit housing residents are at risk of secondhand smoke exposure from adjoining units and common areas. We developed this case study to document state-level strategies undertaken to address this risk. We explored program documents to identify facilitators, barriers, and outcomes. Three states (Montana, Michigan, and Nebraska) provided detailed information on multiunit housing efforts in the study time frame. We conducted a qualitative analysis using inductive coding to develop themes. Several facilitators relating to existing infrastructure included traditional and nontraditional partnerships, leadership and champions, collecting and using data, efficient use of resources, and strategic plans. We also report external catalysts, barriers, and outcomes. Significant state leadership and effort were required to provide local-level technical assistance to engage traditional and nontraditional partners. Information needs were identified and varied by stakeholder type (i.e., health vs. housing). States recommend starting with public housing authorities, so they can become resources for affordable and subsidized housing. These lessons and resources can be used to inform smoke-free multiunit housing initiatives in other states and localities.

INTRODUCTION: Electronic nicotine delivery system (ENDS) use has increased rapidly in the U.S. in recent years. The availability and use of ENDS raise new issues for public health practice and tobacco regulation, as it is unknown whether patterns of ENDS use enhance, deter, or have no impact on combustible tobacco product use. This study assessed past-month, lifetime, and frequency of ENDS use among current, former, and never adult cigarette smokers. METHODS: Data were analyzed from the 2014 Styles, a national consumer-based probability-based web panel survey of U.S. adults aged ≥18 years (n=4,269) conducted during June and July. Lifetime ENDS users were defined as those who reported having used ENDS ≥1 day in their lifetime. Past-month ENDS users were defined as those who reported using ENDS in the past 30 days. RESULTS: In 2014, overall lifetime and past-month ENDS use was 14.1% and 4.8%, respectively. By smoking status, 49.5% of current, 14.7% of former, and 4.1% of never cigarette smokers had used ENDS in their lifetime, whereas 20.6% of current, 4.0% of former, and 0.8% of never smokers used ENDS in the past month. Among current and former cigarette smokers who ever used ENDS, 44.1% and 44.7% reported using ENDS >10 days in their lifetime, respectively. CONCLUSIONS: Because the effect ENDS use has on combustible tobacco products use is unknown, and lifetime and past-month ENDS use is more common among current than former or never smokers, continued surveillance of ENDS use among adults is critical to programs and policies.

OBJECTIVES: We assessed whether smoking cessation improved among pregnant smokers who attended Women, Infants and Children (WIC) Supplemental Nutrition Program clinics trained to implement a brief smoking cessation counseling intervention, the 5As: ask, advise, assess, assist, arrange. METHODS: In Ohio, staff in 38 WIC clinics were trained to deliver the 5As from 2006 through 2010. Using 2005-2011 Pregnancy Nutrition Surveillance System data, we performed conditional logistic regression, stratified by clinic, to estimate the relationship between women's exposure to the 5As and the odds of self-reported quitting during pregnancy. Reporting bias for quitting was assessed by examining whether differences in infants' birth weight by quit status differed by clinic training status. RESULTS: Of 71,526 pregnant smokers at WIC enrollment, 23% quit. Odds of quitting were higher among women who attended a clinic after versus before clinic staff was trained (adjusted odds ratio, 1.16; 95% confidence interval, 1.04-1.29). The adjusted mean infant birth weight was, on average, 96g higher among women who reported quitting (P<0.0001), regardless of clinic training status. CONCLUSIONS: Training all Ohio WIC clinics to deliver the 5As may promote quitting among pregnant smokers, and thus is an important strategy to improve maternal and child health outcomes.

We identified and described strategies for promoting smoking cessation and smoke-free environments that were implemented in Oregon and Utah in treatment centers for mental illness and substance abuse. We reviewed final evaluation reports submitted by state tobacco control programs (TCPs) to the Centers for Disease Control and Prevention and transcripts from a call study evaluation. The TCPs described factors that assisted in implementing strategies: being ready for opportunity, having a sound infrastructure, and having a branded initiative. These strategies could be used by other programs serving high-need populations for whom evidence-based interventions are still being developed.

PURPOSE: Youth are exposed to many types of protobacco influences, including smoking in movies, which has been shown to cause initiation. This study investigates associations between different channels of protobacco media and susceptibility to smoking cigarettes, cigarette experimentation, and current tobacco use among US middle and high school students. METHODS: By using data from the 2012 National Youth Tobacco Survey, structural equation modeling was performed in 2013. The analyses examined exposure to tobacco use in different channels of protobacco media on smoking susceptibility, experimentation, and current tobacco use, accounting for perceived peer tobacco use. RESULTS: In 2012, 27.9% of respondents were never-smokers who reported being susceptible to trying cigarette smoking. Cigarette experimentation increased from 6.3% in 6th grade to 37.1% in 12th grade. Likewise, current tobacco use increased from 5.2% in 6th grade to 33.2% in 12th grade. Structural equation modeling supported a model in which current tobacco use is associated with exposure to static advertising through perception of peer use, and by exposure to tobacco use depicted on TV and in movies, both directly and through perception of peer use. Exposure to static advertising appears to directly increase smoking susceptibility but indirectly (through increased perceptions of peer use) to increase cigarette experimentation. Models that explicitly incorporate peer use as a mediator can better discern the direct and indirect effects of exposure to static advertising on youth tobacco use initiation. CONCLUSIONS: These findings underscore the importance of reducing youth exposure to smoking in TV, movies, and static advertising.

OBJECTIVES: In 2006, the state of Ohio initiated the implementation of a brief smoking cessation intervention (5As: Ask, Advise, Assess, Assist, and Arrange) in select public health clinics that serve low-income pregnant and post-partum women. Funds later became available to expand the program statewide by 2015. However, close to half of the clinics initially trained stopped implementation of the 5As. To help guide the proposed statewide expansion plan for implementation of the 5As, this study assessed barriers and facilitators related to 5As implementation among clinics that had ever received training. METHODS: A mixed-methods approach was used, comprising semi-structured interviews with clinic program directors (n = 21) and a survey of clinic staff members (n = 120), to assess implementation-related barriers, facilitators, training needs, and staff confidence in delivering the 5As. RESULTS: Semi-structured interviews of program directors elucidated implementation barriers including time constraints, low self-efficacy in engaging resistant clients, and paperwork-related documentation challenges. Facilitators included availability of community referral resources, and integration of cessation interventions into the clinic workflow. Program directors believed they would benefit from more hands-on training in delivering the 5As. The survey results showed that a majority of staff felt confident advising (61 %) or referring clients for tobacco dependence treatment (74 %), but fewer felt confident about discussing treatment options with clients (29 %) or providing support to clients who had relapsed (30 %). CONCLUSIONS: Time constraints and documentation issues were major barriers to implementing the 5As. Simplified documentation processes and training enhancements, coupled with systems change, may enhance delivery of evidence-based smoking cessation interventions.

INTRODUCTION: Until recently, in-language telephone quitline services for smokers who speak Asian languages were available only in California. In 2012, the Centers for Disease Control and Prevention (CDC) funded the national Asian Smokers' Quitline (ASQ) to expand this service to all states. The objective of this study was to examine characteristics of ASQ callers, how they heard about the quitline, and their use of the service. METHODS: Characteristics of callers from August 2012 through July 2014 were examined by using descriptive statistics. We examined demographics, cigarette smoking status, time to first cigarette, how callers heard about the quitline, and service use (receipt of counseling and medication) by using ASQ intake and administrative data. We analyzed these data by language and state. RESULTS: In 2 years, 5,771 callers from 48 states completed intake; 31% were Chinese (Cantonese or Mandarin), 38% were Korean, and 31% were Vietnamese. More than 95% of all callers who used tobacco were current daily cigarette smokers at intake. About 87% of ASQ callers were male, 57% were aged 45 to 64 years, 48% were uninsured, and educational attainment varied. Most callers (54%) were referred by newspapers or magazines. Nearly all eligible callers (99%) received nicotine patches. About 85% of smokers enrolled in counseling; counseled smokers completed an average of 4 sessions. CONCLUSION: ASQ reached Chinese, Korean, and Vietnamese speakers nationwide. Callers were referred by the promotional avenues employed by ASQ, and most received services (medication, counseling, or both). State quitlines and local organizations should consider transferring callers and promoting ASQ to increase access to cessation services.