Racial Disparities in Flavored Tobacco Product Use, Curiosity, Susceptibility, and Harm Perception, National Youth Tobacco Survey 2019-2020.

Introduction: Studies characterizing differences in youth flavored tobacco product use prevalence, curiosity/susceptibility, and harm perceptions by race and ethnicity are limited. This study comprehensively examines flavored tobacco product use and harm perceptions among U.S. middle and high school students, by race and ethnicity. Methods: Data came from the 2019 (N=19,018) and 2020 (N=14,531) National Youth Tobacco Surveys (NYTS). Weighted prevalence estimates of flavored tobacco product use and curiosity, susceptibility, and harm perception are reported by race and ethnicity (non-Hispanic [NH] White, NH Black, Hispanic, or NH Other). t-Tests assessed differences in prevalence by years and racial/ethnic groups. Results: Among youth with past 30-day tobacco use, use of most flavored tobacco products increased across all racial/ethnic groups; the largest increase was observed among Hispanic youth using other flavored tobacco products (30.3%). The group with the highest susceptibility to future electronic cigarette (e-cigarette) use was Hispanic students (42.3%). Hispanic students had the highest curiosity about and susceptibility to future use of cigarettes and cigars as well. Conclusions: Increases in the use of and higher susceptibility to other flavored tobacco products, particularly among Hispanic youth, suggest a need for additional changes in environmental conditions and possibly targeted or tailored tobacco control interventions for Hispanic youth. Implications: Given that flavored tobacco use is prevalent among youth and aggressively marketed more to racial/ethnic minority populations, it is important to understand how susceptibility and perceptions relate to tobacco use. Our results suggest a need for a better understanding of social and environmental factors that drive tobacco use behaviors and perceptions, particularly among Hispanic youth, to address the root causes of these differences and create more equitable tobacco control interventions.

Direct intramyocardial injection of VEGF mRNA in patients undergoing coronary artery bypass grafting.

Vascular endothelial growth factor A (VEGF-A) has therapeutic cardiovascular effects, but delivery challenges have impeded clinical development. We report the first clinical study of naked mRNA encoding VEGF-A (AZD8601) injected into the human heart. EPICCURE (ClinicalTrials.gov: NCT03370887) was a randomized, double-blind study of AZD8601 in patients with left ventricular ejection fraction (LVEF) 30%-50% who were undergoing elective coronary artery bypass surgery. Thirty epicardial injections of AZD8601 (total 3 mg) or placebo in citrate-buffered saline were targeted to ischemic but viable myocardial regions mapped using quantitative [15O]-water positron emission tomography. Seven patients received AZD8601 and four received placebo and were followed for 6 months. There were no deaths or treatment-related serious adverse events and no AZD8601-associated infections, immune reactions, or arrhythmias. Exploratory outcomes indicated potential improvement in LVEF, Kansas City Cardiomyopathy Questionnaire scores, and N-terminal pro-B-type natriuretic peptide levels, but the study is limited in size, and significant efficacy conclusions are not possible from the dataset. Naked mRNA without lipid encapsulation may provide a safe delivery platform for introducing genetic material to cardiac muscle, but further studies are needed to confirm efficacy and safety in a larger patient pool.

Disparities in Current Cigarette Smoking Among US Adults With Mental Health Conditions.

INTRODUCTION: Prevalence of cigarette smoking is disproportionally high among US adults with mental health conditions. Adults with mental health conditions who smoke cigarettes are at increased risk for smoking-related illness and death compared with adults without mental health conditions. METHODS: We analyzed pooled data from the 2019 and 2020 National Survey on Drug Use and Health to provide national estimates of current cigarette smoking prevalence among US adults aged 18 years or older who reported having in the past year any mental illness, serious mental illness, mild or moderate mental illness, serious psychological distress, and/or major depressive episode (N = 19,398) and state-level estimates for any mental illness. RESULTS: Prevalence of cigarette smoking for serious mental illness was 27.2%; serious psychological distress and major depressive disorder, 25.0%; serious psychological distress, 24.5%; any mental illness, 22.8%; mild or moderate mental illness, 21.2%; and major depressive disorder, 17.6%. State-level cigarette smoking prevalence among adults with any mental illness ranged from 11.7% in Utah to 42.1% in Louisiana, with a median of 24.7%. CONCLUSION: The prevalence of current cigarette smoking is higher among adults with any mental illness, psychological distress, and major depressive disorder than among those without any mental illness, especially among adults who are non-Hispanic American Indian or Alaska Native, Hispanic, lesbian, gay, or bisexual and among those who are experiencing poverty, are uninsured, or have been arrested and booked in the past year. Continued improvement in integration of smoking cessation interventions into mental health treatment, equitable implementation of comprehensive commercial tobacco control policies, and population-specific approaches could reduce cigarette smoking among adults with mental health conditions.

Substance use among adult marijuana and nicotine e-cigarette or vaping product users, 2020.

INTRODUCTION: Co-use of marijuana and tobacco/nicotine have unknown impacts on addiction and health. There are limited data on the extent to which adults are co-using tetrahydrocannabinol (THC)- and nicotine-containing products, in any of their various modes. This study describes adult use of THC- and nicotine-containing products among electronic vaping product (EVP) users. METHODS: Data on marijuana and tobacco use were collected from February 25-29, 2020 through an online survey of adults aged ≥18 years who reported using THC- and nicotine-containing electronic vaping products (EVPs) in the past 3 months (n = 3,980). Survey respondents from 18 states participated in the U.S. YouGov panel, a proprietary opt-in internet panel survey of 1.8 million U.S. residents. RESULTS: Among those who reported using nicotine and THC-containing EVPs in the past 3 months, 90.1% of respondents reported smoking marijuana in the past 3 months; 82.7% reported smoking as the most frequent mode of marijuana use. Almost 63% of EVP users reported smoking cigarettes; 55.6% reported smoking for over 8 years, while 7.7% had been smoking cigarettes for under a year. CONCLUSIONS: In this study, respondents reported cigarette smoking and marijuana smoking in addition to using marijuana- and nicotine- containing EVPs. Considering the unknown health effects of co-use of tobacco and THC-containing products, the finding that adults are vaping THC and nicotine alongside traditional modes of marijuana and tobacco use of these substances warrants further investigation. IMPLICATIONS: Findings from this study provide evidence that adults who use nicotine and THC EVPs are also using a variety of other THC-containing and tobacco-containing products. This indicates the importance of continued surveillance to assess trends of polysubstance EVP and multi-modal marijuana and tobacco use. Monitoring various modes of marijuana and tobacco use may inform policies, prevention education, communication, and cessation tools.

Tetrahydrocannabinol (THC)-containing e-cigarette, or vaping, product use behaviors among adults after the onset of the 2019 outbreak of e-cigarette, or vaping, product use-associated lung injury (EVALI).

INTRODUCTION: During the E-cigarette, or Vaping, Product Use-Associated Lung Injury (EVALI) outbreak, patient data on tetrahydrocannabinol (THC)-containing e-cigarette, or vaping, product (EVP) use was collected, but data on non-affected adult product use after the onset of the EVALI outbreak is limited. This study describes adult THC-EVP use after EVALI began. METHODS: THC-EVP use data came from an 18-state web-based panel survey of adult THC- and nicotine-containing EVP users conducted February 2020. Unweighted descriptive statistics were calculated; logistic regression assessed correlates of use. RESULTS: Among 3,980 THC-EVP users, 23.5% used THC-EVPs daily. Common brands of THC-EVPs used were Dank Vapes (47.7%) and Golden Gorilla (38.7%). Reported substances used included THC oils (69.6%), marijuana herb (63.6%) and THC concentrate (46.4%). Access sources included: recreational dispensaries (41.1%), friend/family member (38.6%) and illicit dealers (15.1%). Respondents aged 45-64 years had lower odds for daily use compared with those aged 25-34 years (aOR = 0.73; 95% CI = 0.60, 0.90). Compared with White respondents, Asian respondents had lower odds (aOR = 0.55; 95% CI = 0.36, 0.84) and Black respondents higher odds (aOR = 1.48; 95% CI = 1.17, 1.86) of daily use. Respondents odds of daily use and accessing THC-EVPs through commercial sources were higher among states with legalized nonmedical adult marijuana use compared to states without. CONCLUSIONS: Almost half of respondents reported daily or weekly THC-EVP use, and accessed products through both informal and formal sources, even after EVALI began. Given the potential for future EVALI-like conditions to occur, it is important to monitor the use of THC-EVPs and ensure effective education activities about associated risk.

Differences in rapid increases in county-level COVID-19 incidence by implementation of statewide closures and mask mandates - United States, June 1-September 30, 2020.

BACKGROUND AND OBJECTIVE: Community mitigation strategies could help reduce COVID-19 incidence, but there are few studies that explore associations nationally and by urbanicity. In a national county-level analysis, we examined the probability of being identified as a county with rapidly increasing COVID-19 incidence (rapid riser identification) during the summer of 2020 by implementation of mitigation policies prior to the summer, overall and by urbanicity. METHODS: We analyzed county-level data on rapid riser identification during June 1-September 30, 2020 and statewide closures and statewide mask mandates starting March 19 (obtained from state government websites). Poisson regression models with robust standard error estimation were used to examine differences in the probability of rapid riser identification by implementation of mitigation policies (P-value< .05); associations were adjusted for county population size. RESULTS: Counties in states that closed for 0-59 days were more likely to become a rapid riser county than those that closed for >59 days, particularly in nonmetropolitan areas. The probability of becoming a rapid riser county was 43% lower among counties that had statewide mask mandates at reopening (adjusted prevalence ratio = 0.57; 95% confidence intervals = 0.51-0.63); when stratified by urbanicity, associations were more pronounced in nonmetropolitan areas. CONCLUSIONS: These results underscore the potential value of community mitigation strategies in limiting the COVID-19 spread, especially in nonmetropolitan areas.

Decline in COVID-19 Hospitalization Growth Rates Associated with Statewide Mask Mandates - 10 States, March-October 2020.

SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), is transmitted predominantly by respiratory droplets generated when infected persons cough, sneeze, spit, sing, talk, or breathe. CDC recommends community use of face masks to prevent transmission of SARS-CoV-2 (1). As of October 22, 2020, statewide mask mandates were in effect in 33 states and the District of Columbia (2). This study examined whether implementation of statewide mask mandates was associated with COVID-19-associated hospitalization growth rates among different age groups in 10 sites participating in the COVID-19-Associated Hospitalization Surveillance Network (COVID-NET) in states that issued statewide mask mandates during March 1-October 17, 2020. Regression analysis demonstrated that weekly hospitalization growth rates declined by 2.9 percentage points (95% confidence interval [CI] = 0.3-5.5) among adults aged 40-64 years during the first 2 weeks after implementing statewide mask mandates. After mask mandates had been implemented for ≥3 weeks, hospitalization growth rates declined by 5.5 percentage points among persons aged 18-39 years (95% CI = 0.6-10.4) and those aged 40-64 years (95% CI = 0.8-10.2). Statewide mask mandates might be associated with reductions in SARS-CoV-2 transmission and might contribute to reductions in COVID-19 hospitalization growth rates, compared with growth rates during <4 weeks before implementation of the mandate and the implementation week. Mask-wearing is a component of a multipronged strategy to decrease exposure to and transmission of SARS-CoV-2 and reduce strain on the health care system, with likely direct effects on COVID-19 morbidity and associated mortality.

Associations between select blood VOCs and hematological measures in NHANES 2005-2010.

Exposure to VOCs is linked to health effects ranging from asthma to cancer and to negative impacts on the hematopoietic system. We examined the association between select blood VOC concentrations and hematological measures in a representative sample of the U.S. population from NHANES cycles spanning the years 2005 to 2010. We used Cox regression to assess the association between complete blood count with five-part differential (CBC) parameters and seven select blood VOCs, while addressing low detection rates among VOCs. Tobacco smoke exposure was classified using serum cotinine levels. The not-smoke-exposed group had lower VOC levels for most analytes compared with the smoke-exposed. Correlations between benzene, toluene, ethylbenzene, and xylenes (BTEX) were moderate to strong. Statistical associations were found between benzene, toluene, ethylbenzene, xylene, and styrene (BTEXS) and hematocrit, hemoglobin, and white blood cell count among the smoke-exposed. Among the not-smoke-exposed, there was an association between BTEX and platelet count. We considered benzene most likely to be associated with higher levels of CBC concentrations. Our findings suggest VOC levels currently found in the general U.S. population are associated with changes in hematological measures, and smoking could be a contributor.

Characterization of trace elements exposure in pregnant women in the United States, NHANES 1999-2016.

OBJECTIVE: The objective of the current study is to report on urine, blood and serum metal concentrations to characterize exposures to trace elements and micronutrient levels in both pregnant women and women of child-bearing age in the U.S. National Health and Nutrition Examination Survey (NHANES) years 1999-2016. METHODS: Urine and blood samples taken from NHANES participants were analyzed for thirteen urine metals, three blood metals, three serum metals, speciated mercury in blood and speciated arsenic in urine. Adjusted and unadjusted least squares geometric means and 95% confidence intervals were calculated for all participants among women aged 15-44 years. Changes in exposure levels over time were also examined. Serum cotinine levels were used to adjust for smoke exposure, as smoking is a source of metal exposure. RESULTS: Detection rates for four urine metals from the ATSDR Substance Priority List: arsenic, lead, mercury and cadmium were ~83-99% for both pregnant and non-pregnant women of child bearing age. A majority of metal concentrations were higher in pregnant women compared to non-pregnant women. Pregnant women had higher mean urine total arsenic, urine mercury, and urine lead; however, blood lead and mercury were higher in non-pregnant women. Blood lead, cadmium, mercury, as well as urine antimony, cadmium and lead in women of childbearing age decreased over time, while urine cobalt increased over time. CONCLUSIONS: Pregnant women in the US have been exposed to several trace metals, with observed concentrations for some trace elements decreasing since 1999.

Cigarette Design Features: Effects on Emission Levels, User Perception, and Behavior.

OBJECTIVES: This paper describes the effects of non-tobacco, physical cigarette design features on smoke emissions, product appeal, and smoking behaviors - 3 factors that determine smoker's exposure and related health risks. METHODS: We reviewed available evidence for the impact of filter ventilation, new filter types, and cigarettes dimensions on toxic emissions, smoker's perceptions, and behavior. For evidence sources we used scientific literature and websites providing product characteristics and marketing information. RESULTS: Whereas filter ventilation results in lower machine-generated emissions, it also leads to perceptions of lighter taste and relative safety in smokers who can unwittingly employ more intense smoking behavior to obtain the desired amount of nicotine and sensory appeal. Filter additives that modify smoke emissions can also modify sensory cues, resulting in changes in smoking behavior. Flavor capsules increase the cigarette's appeal and novelty, and lead to misperceptions of reduced harm. Slim cigarettes have lower yields of some smoke emissions, but smoking behavior can be more intense than with standard cigarettes. CONCLUSIONS: Physical design features significantly impact machine-measured emission yields in cigarette smoke, product appeal, smoking behaviors, and exposures in smokers. The influence of current and emerging design features is important in understanding the effectiveness of regulatory actions to reduce smoking-related harm.

Smoking Behavior and Exposure: Results of a Menthol Cigarette Cross-over Study.

OBJECTIVE: Our objective was to improve understanding of the differences in use behavior and exposure when smoking menthol and non-menthol cigarettes using a 2-part cross-over design. METHODS: Adult daily smokers were assigned randomly to alternate between 2 weeks of exclusively smoking a menthol test cigarette or a non-menthol test cigarette. Urine and saliva were collected for biomarker measurements; carbon monoxide (CO) was measured, and participants smoked test cigarettes through a CreSS® smoking topography device during 3 clinic visits. Participants turned in their cigarette butts from the test periods for determination of mouth level nicotine and completed subjective questionnaires related to the test cigarettes. RESULTS: Regardless of cigarette preference, participants had higher salivary cotinine when smoking the non-menthol test cigarette, but there were no significant differences detected in urine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol between the 2 test cigarettes. Mouth level nicotine, puff volume, and puff duration were significantly higher when smoking the menthol brand. Both menthol and non-menthol smokers reported significantly lower enjoyment and satisfaction scores for test cigarettes compared with their brand of choice. CONCLUSIONS: Our results suggest that mentholation has an effect on measures of smoking behavior and that mouth level nicotine is a useful indicator of between-brand smoke exposure.

Quantitative analysis of menthol in human urine using solid phase microextraction and stable isotope dilution gas chromatography-mass spectrometry.

To accurately measure menthol levels in human urine, we developed a method using gas chromatography/electron ionization mass spectrometry with menthol-d4 stable isotope internal standardization. We used solid phase microextraction (SPME) headspace sampling for collection, preconcentration and automation. Conjugated forms of menthol were released using ß-glucuronidase/sulfatase to allow for measuring total menthol. Additionally, we processed the specimens without using ß-glucuronidase/sulfatase to quantify the levels of unconjugated (free) menthol in urine. This method was developed to verify mentholated cigarette smoking status to study the influence of menthol on smoking behaviour and exposure. This objective was accomplished with this method, which has no carryover or memory from the SPME fiber assembly, a method detection limit of 0.0017µg/mL, a broad linear range of 0.002-0.5µg/mL for free menthol and 0.01-10µg/mL for total menthol, a 7.6% precision and 88.5% accuracy, and an analysis runtime of 17min. We applied this method in analysis of urine specimens collected from cigarette smokers who smoke either mentholated or non-mentholated cigarettes. Among these smokers, the average total urinary menthol levels was three-fold higher (p<0.001) among mentholated cigarette smokers compared with non-mentholated cigarette smokers.

Method for the Determination of Ammonia in Mainstream Cigarette Smoke Using Ion Chromatography.

Ammonia in mainstream smoke is present in both the particulate and vapor phases. The presence of ammonia in the cigarette filler material and smoke is of significance because of the potential role ammonia could have in raising the "smoke pH." An increased smoke pH could shift a fraction of total nicotine to free-base nicotine, which is reportedly more rapidly absorbed by the smoker. Methods measuring ammonia in smoke typically employ acid filled impingers to trap the smoke. We developed a fast, reliable method to measure ammonia in mainstream smoke without the use of costly and time consuming impingers to examine differences in ammonia delivery. The method uses both a Cambridge filter pad and a Tedlar bag to capture particulate and vapor phases of the smoke. We quantified ammonia levels in the mainstream smoke of 50 cigarette brands from 5 manufacturers. Ammonia levels ranged from approximately 1µg to 23µg per cigarette for ISO smoking conditions and 38µg to 67µg per cigarette for Canadian intense smoking conditions and statistically significance differences were observed between brands and manufacturers. Our findings suggest that ammonia levels vary by brand and are higher under Canadian intense smoking conditions.

Method for the determination of ammonium in cigarette tobacco using ion chromatography.

Ammonia and other alkaline substances have been postulated to be important in cigarette design. The most significant potential contribution of ammonia is a possible interaction with the native, protonated nicotine in the smoke. Ammonia is more alkaline than nicotine and could facilitate a shift in the acid/base equilibrium where a fraction of the total nicotine converts to the more lipophilic, non-protonated form. This non-protonated, or free-base, form of nicotine absorbs more efficiently across membranes, resulting in more rapid delivery to the smoker's bloodstream. Ammonia and other potential ammonia sources, such as additives like diammonium phosphate, could influence the acid-base dynamics in cigarette smoke and ultimately the rate of nicotine delivery. To examine and characterize the ammonia content in modern cigarettes, we developed a fast, simple and reliable ion chromatography based method to measure extractable ammonia levels in cigarette filler. This approach has minimal sample preparation and short run times to achieve high sample throughput. We quantified ammonia levels in tobacco filler from 34 non-mentholated cigarette brands from 3 manufacturers to examine the ranges found across a convenience sampling of popular, commercially available domestic brands and present figures of analytical merit here. Ammonia levels ranged from approximately 0.9 to 2.4mg per gram of cigarette filler between brands and statistically significance differences were observed between brands and manufacturers. Our findings suggest that ammonia levels vary by brand and manufacturer; thus in domestic cigarettes ammonia could be considered a significant design feature because of the potential influence on smoke chemistry.

Chemical analysis of Alaskan Iq'mik smokeless tobacco.

INTRODUCTION: Iq'mik, a form of smokeless tobacco (ST), is traditionally used by Cup'ik and Yup'ik Eskimo people of western Alaska. Iq'mik is sometimes incorrectly considered to be a healthier alternative to smoking because its ingredients are perceived as "natural." Our chemical characterization of iq'mik shows that iq'mik is not a safe alternative to smoking or other ST use. METHODS: We measured nicotine and pH levels of tobacco and ash used to prepare iq'mik. We also characterized levels of toxins which are known to be present in ST including tobacco-specific nitrosamines (TSNAs) and polycyclic aromatic hydrocarbons (PAHs) using chromatographic separations coupled with isotope dilution mass spectrometry. RESULTS: Nicotine content in the iq'mik tobacco was very high, ranging from 35 to 43 mg/g, with a mean of 39 mg/g. The pH of the iq'mik tobacco-ash mixture was 11, an extremely high level compared with most ST products. High levels of PAHs were seen in the fire-cured tobacco samples with a benzo[a]pyrene level of 87 ng/g. Average TSNA levels in the tobacco were 34, 2,700, and 340 ng/g for 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), N'-nitrosonornicotine (NNN), and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), respectively. CONCLUSIONS: Iq'mik contains high levels of the more easily absorbed unionized nicotine as well as known carcinogenic TSNAs and PAHs. The perception that iq'mik is less hazardous than other tobacco products due to the use of "natural" ingredients is not warranted. This chemical characterization of iq'mik gives a better understanding of the risk of possible adverse health effects of its use.