Nonsmoking Adults Research Articles

Novel Insights into Young Adults' Perceived Effectiveness of Waterpipe Tobacco-Specific Pictorial Health Warning Labels in Lebanon: Implications for Tobacco Control Policy.

This study aims to explore the perceived effectiveness of waterpipe (WP) tobacco specific health warning labels (HWLs) among young adult WP smokers and nonsmokers in Lebanon. Before participating in focus group discussions, participants (n = 66; WP smokers n = 30; nonsmokers n = 36; age 18–33) completed a brief survey to rate the effectiveness of 12 HWLs’ and rank them according to four risk themes (WP health effects, WP harm to others, WP-specific harm, and WP harm compared to cigarettes). Differences in HWLs ratings by WP smoking status were examined and the top-ranked HWL in each theme were identified. HWLs depicting mouth cancer and harm to babies were rated as the most effective by both WP smokers and non-smokers. WP smokers rated HWLs which depicted harm to children and infants as more effective than non-smokers. The top-ranked HWLs for perceived overall effectiveness were those depicting “oral cancer”, “harm to babies”, “orally transmitted diseases” and “mouth cancer”. HWLs depicting oral lesions and harm to babies were rated as most effective, while HWLs showing the harmful effects of WP secondhand smoke on infants and children were rated as less effective by nonsmokers compared to smokers. Our study provides evidence on the potential effectiveness of HWLs for further evaluation in Lebanon and the Eastern Mediterranean region. The results will inform and guide the development and implementation of tobacco control policy.

Abstract CT125: Evaluation of potential drug-drug interactions (DDIs) between futibatinib and CYP3A inhibitors/inducers, CYP3A substrates, or proton pump inhibitors (PPIs)

Abstract Background Futibatinib is an oral, irreversible FGFR1-4 inhibitor with clinical activity in cholangiocarcinoma and other FGFR-aberrant tumors. The recommended futibatinib dosage is 20 mg once daily (QD). In vitro studies have shown that futibatinib is predominantly metabolized by and inhibits cytochrome p450 3A (CYP3A); futibatinib is also a P-glycoprotein substrate. Two phase 1 studies were performed in healthy volunteers to evaluate potential DDIs between futibatinib and CYP3A substrates (midazolam; study 1) or CYP3A inhibitors/inducers (itraconazole/rifampin; study 2). As the solubility of futibatinib is pH dependent, study 3 assessed the effect of PPI (lansoprazole) coadministration on futibatinib pharmacokinetics (PK). Methods All 3 studies, conducted in adult nonsmokers, were open-label, fixed-sequence, 2-period cross-over studies with a 1- or 2-d washout between each period. In study 1, midazolam 2 mg was given on d1 of period 1 (-futibatinib) and on d7 of period 2 (+futibatinib 20 mg QD d1-7). In study 2, futibatinib 20 mg was given on d1 of period 1 (alone) and on d5 (+itraconazole 200 mg QD d1-6) or d8 (+rifampin 600 mg QD d1-9) of period 2. In study 3, futibatinib 20 mg was given on d1 of period 1 (-lansoprazole) and d5 of period 2 (+lansoprazole 60 mg QD d1-5). Plasma samples for PK assessment were collected predose through 24 h post-midazolam dosing (study 1) and predose through 48 h post-futibatinib dosing (studies 2 and 3). Results In study 1 (N=24), coadministration of futibatinib did not result in clinically significant changes in midazolam PK, based on the area under the concentration curve extrapolated to the last measurable time (AUC0-t; -9%) or infinity (AUC0-inf; -9%) or maximum plasma concentration (Cmax; -5%), compared with midazolam alone. In study 2 (N=40), relative to futibatinib administered alone, coadministration with itraconazole increased futibatinib Cmax (+51%) and plasma exposure (AUC0-t and AUC0-inf +41% each), whereas coadministration with rifampin decreased futibatinib Cmax (-53%) and plasma exposure (AUC0-t and AUC0-inf -64% each). In study 3 (N=20), coadministration of lansoprazole did not result in clinically significant changes in futibatinib PK parameters vs futibatinib alone (AUC0-t +5%; AUC0-inf +5%; Cmax +8%). Agents were well tolerated, and all 3 studies were completed with no clinically relevant safety signals. Conclusions Futibatinib is not expected to affect the exposure of concomitant medications metabolized via CYP3A, the most common drug metabolism pathway. Caution should be exercised when coadministering strong CYP3A inducers or inhibitors with futibatinib, as significant DDIs were observed with itraconazole and rifampin. Futibatinib can be concomitantly administered with PPIs with no clinically relevant impact on futibatinib exposure. Citation Format: Ikuo Yamamiya, John Laabs, Allen Hunt, Toru Takenaka, Daryl Sonnichsen, Mark Mina, Yaohua He, Karim Benhadji. Evaluation of potential drug-drug interactions (DDIs) between futibatinib and CYP3A inhibitors/inducers, CYP3A substrates, or proton pump inhibitors (PPIs) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT125.

Abstract CT128: Effect of futibatinib on QT/QTc interval: a randomized, controlled, double-blind study

Abstract Background Futibatinib is an oral selective irreversible FGFR inhibitor with clinical activity in cholangiocarcinoma and other FGFR-deregulated tumors. A phase 1 thorough QT study was conducted to evaluate the effect of futibatinib on the heart rate (HR)-corrected QT (QTc) interval. Methods Healthy nonsmoking adults 18-55 years of age were randomized to receive single doses of each of the following treatments in different sequences: futibatinib (20 or 80 mg [therapeutic and supratherapeutic doses, respectively]), placebo, or moxifloxacin (positive QTc-prolongation control; 400 mg). At least 7 days were allowed between administration of each of the 4 treatments. Administration of futibatinib and placebo was double-blind; that of moxifloxacin was open-label. The primary endpoint was the difference in change from baseline in QTcF (QT interval corrected using Fridericia's formula) between futibatinib and placebo (ddQTcF) at the time points tested. Upper limits of the 2-sided 90% confidence intervals (CIs) of these differences of <10 ms indicated lack of QTc prolongation (per ICH E14 guidance). Secondary endpoints included change from baseline in other electrocardiogram (ECG) parameters, pharmacokinetics (PK), and safety. Results Enrolled participants (N=48) received ≥1 dose of futibatinib, were evaluable for futibatinib PK, and were included in the analysis population. The ddQTcF ranged from 0.13 to 2.47 ms with 20 mg futibatinib and from -0.04 to 2.46 ms with 80 mg futibatinib from 0.5 to 24 h after dosing. Upper limits of the 2-sided 90% CIs of these values remained well below 10 ms (<5 ms) throughout. The lower limits of 2-sided 97.5% CIs of the difference in change from baseline in QTcF between moxifloxacin and placebo all exceeded 5 ms (8.06-11.43 ms) at the time points analyzed (1.5, 2, 3, and 4 h), demonstrating assay sensitivity. No clinically significant effects of futibatinib on HR, other ECG parameters (eg, PR, QRS, or QT intervals), or ECG morphology were identified. Exposure-response modeling indicated no significant relationship between plasma futibatinib concentration and the QTcF interval. The futibatinib area under the concentration curve from time 0 to infinity and maximum plasma concentration (Cmax) increased by 4.5- and 3.3-fold, respectively, after administration of a single dose of 80 vs 20 mg. The Cmax values observed with 80 mg futibatinib (median, 553 ng/mL; range, 71-1160) exceeded any Cmax observed or expected with the 20-mg daily therapeutic dose at steady state. Seven participants (15%) experienced adverse events of any cause after receiving either futibatinib dose, all grade 1/2. Conclusions A single therapeutic or supratherapeutic dose of futibatinib did not prolong the QTc interval or adversely affect other measures of heart function. Futibatinib exposure increased dose-dependently, and administration was safe and well tolerated in healthy participants. Citation Format: Ikuo Yamamiya, John Laabs, Daryl Sonnichsen, Mark Mina, Yaohua He, Karim Benhadji. Effect of futibatinib on QT/QTc interval: a randomized, controlled, double-blind study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT128.

Examining the effect of waterpipe specific pictorial health warning labels among young adults in Lebanon and Tunisia: Protocol of a factorial experiment study design

BackgroundWaterpipe tobacco smoking (WTS) has increased substantially in the Eastern Mediterranean Region (EMR), affecting young adults who perceive waterpipe as safer than cigarette smoking. Applying pictorial health warning labels (HWLs) on tobacco products has been effective in communicating health risks associated with tobacco smoking. However, there are few experimental studies that examined pictorial HWLs specific to WTS. Methods/design: This report describes the design and protocol of the first factorial experimental study that aims to test the effectiveness of pictorial HWLs based on their placement on waterpipe device, tobacco, and charcoal packages among young adult smokers and non-smokers residing in Lebanon and Tunisia. After completing a baseline assessment, participants will be randomly assigned to 3 experimental conditions in a 3 (HWL: pictorial HWL on tobacco package vs. pictorial HWL on 3 placements [device, tobacco, and charcoal packages] vs. text-only HWL on tobacco package) x 4 (pictorial HWLs) x 2 (waterpipe smokers vs. non-smokers) factorial design. We will use a within/between-subject design, where pictorial HWLs and time (pre vs. post-exposure) are the within-subject factors and waterpipe smoking status as the between-subjects factor. Participants will complete post-exposure measures that include attention, perceived harm, intention to quit (smokers) or initiate smoking (non-smokers). Discussion: This is the first international study examining the placements of pictorial HWLs using efficient within/between subject design. Findings will provide additional evidence to convince policymakers to consider three placements of HWLs specific to WTS as a promising regulatory target to curb WTS.

Abstract P201: Early Life Exposure To Environmental Tobacco Smoke And Cardiometabolic Diseases In Middle Age: A 4-decade Follow-up Study Of The Collaborative Perinatal Project

Introduction: Environmental tobacco smoke (ETS) is a major source of indoor air pollution and has been associated with cardiovascular diseases (CVD) risks. There is little research on the associations of ETS exposure in early life with CVD risks in later life. Hypothesis: We hypothesized that ETS exposures in the uterus, childhood, and teenage increase midlife CVD risks. Methods: For 1,623 offspring born in 1959-1966 at two sites from the Collaborative Perinatal Project, we defined intrauterine ETS exposure in each trimester if the mother smoked (1-19 or ≥20 cigs/day). ETS exposure in each year from birth to 18 years was quantified by total daily-average hours of parents smoking weighted by daily packs from a questionnaire at the adult follow-up (mean age: 39 years). Ever diagnoses of diabetes (cumulative incidence: 3.0%), heart diseases (1.5%), hypertension (17.3%), and high cholesterol (25.3%) until adult follow-up were reported. Cardiometabolic diseases (CMD, cumulative incidence: 35.4%) were defined as any diagnosis. We estimated odds ratio (OR) for CMD by ETS exposures in each trimester adjusting for prenatal factors (maternal SES, pre-pregnancy BMI, parity, newborn sex); additionally adjusted for maternal smoking in pregnancy, birth weight, and gestational age for ETS exposure from birth to 18 years. We also stratified the analyses by adult smoking status. Results: Exposure to ≥20 cigs/day in the 1 st (OR: 1.52, 95% CI: 1.02-2.26) and 2 nd (OR: 1.50, 95% CI: 1.01-2.24) trimester was significantly associated with hypertension compared to none exposure, and the associations were stronger in adult offspring who were smokers. Among the 70% of participants who reported childhood ETS exposure, the average exposure was 8.5 smoker-hours/day and 10.5 smoker-hour*packs/day (HP/Day), with a declining trend from birth to 18 years. ETS exposure (per SD increment) in early life from birth to 18 years, separately or cumulatively (OR=1.24, 95% CI: 1.07-1.43), was associated with higher odds of adult hypertension. ETS exposure in teenage (11-18 years, OR=1.26, 95% CI: 1.05-1.50), but not in childhood (birth to 10 years, OR=1.18, 95% CI: 0.96-1.45), was associated with higher odds of a combination of adult heart disease and diabetes, which was more striking in adult non-smokers than smokers. Odds of adult CMD increased by 13% (95% CI: 1%-28%) for each SD (about 10 HP/Day) increment in ETS in the whole childhood and by 16% (95% CI: 3%-30%) in teenage. The results for smoker-hours/day were similar to those for smoker-hour*packs/day. Conclusions: Intrauterine exposure to maternal smoking and ETS exposures (time and total amount) from birth to 18 years increase the risk of adult hypertension. ETS exposure in early life may also increase the risk of adult cardiometabolic diseases. Teenage may be a sensitive window for elevated risk of adult heart diseases and diabetes associated with ETS exposure.

Stronger Association between Hemoglobin and Blood Pressure in People Bearing GP.Mur Blood Type

GP.Mur, commonly known as Miltenberger subtype III, is a clinically-important red blood cell (RBC) phenotype unique among Southeast Asians (SEA). On the GP.Mur+ erythrocyte membrane, glycophorin B-A-B hybrid protein is expressed, instead of glycophorin B (GPB). Different from GPB that does not have any known function, GP.Mur hybrid protein promotes expression of anion exchanger-1 (AE1) on the RBC membrane and support AE1-relevant physiological functions in GP.Mur+ carriers. In our previous human studies, we unexpectedly uncovered that GP.Mur+ carriers have slightly higher blood pressure (BP) than GP.Mur-negative people. Since AE1 has been implicated a role in modulation of NO bioavailability and hemoglobin (Hb) is a major NO scavenger, we hypothesized that the slightly but significantly higher BP in GP.Mur carriers might be related to Hb-mediated NO processing. Methods With the approval of hospital Institutional Review Board, healthy, non-smoker subjects aged between 20 and 55 were recruited at Taitung MacKay Memorial Hospital (TT-MMH). Besides general physical assessment, recruited subjects were tested for CBC and RBC phenotypes, including GP.Mur. Results 345 male and 515 female non-smoker adults were recruited from Taitung County, Taiwan, and 22.1% of them bear GP.Mur blood type. For male and female cohorts, GP.Mur erythrocyte expression was significantly associated with slightly higher systolic BP (SBP) (122.2±12.9 mmHg [non-GP.Mur male] versus 127.8±14.4 mmHg [GP.Mur male]; 115.0±13.0 mmHg [non-GP.Mur female] versus 118.0±13.4 mmHg [GP.Mur female]). Hb levels were not affected by GP.Mur. Hb is known to be positively associated with SBP. We indeed found a Pearson correlation of 0.164 between Hb (g/dL) and SBP (mmHg) in non-GP.Mur male subjects (*p~0.007). However, Hb-SBP associations were not observed in our female cohorts with or without GP.Mur. Intriguingly, the Pearson correlation between Hb and SBP from the GP.Mur male group was doubled, compared to that from the GP.Mur-negative male group (Pearson correlation: 0.299 [GP.Mur male] versus 0.164 [non-GP.Mur male]). Conclusion From the differences in Hb-SBP correlations in male, the effects of NO-scavenging by Hb were likely more substantial in the presence of GP.Mur and/or higher AE1 expression. We did not observe any positive associations in our SEA female subjects, presumably due to menstrual cycle and that SEA women were generally more anemic.

The Glycemic Index of Food- Should It Be Gender Specific?

Glycemic index (GI) was developed to categorize dietary carbohydrates based on their overall effect on postprandial blood glucose. Low GI foods demand a lower insulin response compared to high GI foods. This is expected to decrease the incidence of insulin resistance, the development of obesity, and hypertension, which are risk factors for diabetes and cardiovascular disease. Hence, it was recommended to add GI as a valid methodology complementing other dietary aspects that need to be applicable to both genders. In this study, we aimed to investigate the effect of gender difference on GI in healthy, normal BMI males and females. Healthy, non-smoking adults age between 18 -35 years of normal BMI, were recruited. Subjects were included following initial screening using a structured questionnaire and blood tests to exclude diabetes, dyslipidemia, and/or hypertension cases. A standard 50 g glucose tolerance test was performed for two visits for each sugar (glucose and sucrose). Blood was collected at fasting, then at 15,30,45,60,90,120 min after the sugar consumption and the area under the curve was calculated. A total of 11 men and ten women were included in the study after excluding prediabetics and participants with abnormal liver enzymes. The mean GI for the whole sample was 69. A distinctive difference between males and females was noticed in the GI and the response curve. For males, the GI for sucrose was 77, and the response curve peaked at 30 min, followed by a sharp decline below baseline at 2h. On the other hand, the GI for females was 60, and the curve peaked at 45 min. In conclusion, our study showed that there is a clear difference in GI between men and women. A larger study is needed to clarify this further and prove or disprove the need for separate GI lists for men and women.

Effects of transdermal nicotine delivery on cognitive outcomes: A meta-analysis.

By the association of nicotinic acetylcholine receptors in the brain, nicotine in the therapeutic window lowers neuronal damage and raises protective factors. These data, however, are contradicted by other findings. Here, we assessed the effects of transdermal nicotine administration on cognitive functions in healthy non-smoker adults by systematic review and meta-analysis of clinical trials. We included reports of clinical trials comparing the effects of nicotine patches with placebo in healthy non-smoking adults. The main outcome was the impact of nicotine patches on overall cognitive function with a focus on attention and memory. Standard meta-analytic and statistical methods measured the effect of transdermal nicotine compared with placebo patches. We included 31 publications involving 978 subjects. Nicotine patches boosted cognitive function in healthy adults (0.233 SMD, 95%CI, 0.111-0.355, p<.001). Overall heterogeneity of the studies was found to be modest (ϰ2 =68.24, T2 =0.07, I2 =50.17%, p<.001). Also, nicotine patches improved attention (0.231 SMD, 95%CI, 0.106-0.356, p<.001). We found the inter-study heterogeneity to be low (ϰ2 =40.95, T2 =0.03, I2 =34.07%, p=.042). Further, the enhancement of memory by transdermal nicotine did not reach statistical significance in normal subjects (0.270 SMD, 95% CI, -0.293-0.833, p=.347). Also, high inter-study heterogeneity was found among studies (ϰ2 =27.25, T2 =0.43, I2 =77.98%, p<.001). The meta-analysis showed that transdermal nicotine had statistically significant positive effects on attention, and non-significant effects on memory, in healthy non-smoking adults. The results encourage further studies of the therapeutic potential of nicotine patches in disorders of cognition.

Oral tongue squamous cell carcinomas in young patients according to their smoking status: a GETTEC study.

Incidence of oral tongue squamous cell carcinoma (OTSCC) is increasing, especially in young adults, despite decreasing tobacco and alcohol consumption. This multicentric retrospective study of 185 young adults with OTSCC (median follow-up 43months), investigated risk factors, tumour characteristics and oncological outcomes according to the smoking status. Overall, 38% of patients were smokers (S). Non-smokers (NS) were significantly younger than S. Sex ratios were 1.1 for N and 1.8 for S. NS patients were less frequently cannabis or alcohol users than S, but were more likely to have a history of leukoplakia. Second primaries were observed in NS (4.4%) and in S (12.7%). Despite more frequent local relapse in NS (p = 0.018), there was no difference in diagnostic stage and overall survival between groups. OTSCC affects differently young S and NS patients suggesting the existence of a specific clinical entity of OTSCC in non-smoking young adults.

Racial Difference in the Association of Long-Term Exposure to Fine Particulate Matter (PM2.5) and Cardiovascular Disease Mortality among Renal Transplant Recipients.

Ambient air pollutants are known risk factors for cardiovascular disease (CVD) morbidity and mortality with significant racial disparities. However, few studies have explored racial differences among highly susceptible subpopulations, such as renal transplant recipients (RTRs). Despite improvements in quality of life after transplantation, CVD remains the major cause of mortality, especially among Black recipients. This study aimed to evaluate potential racial differences in the association between long-term levels of PM2.5 and the risk of all-cause, total CVD, and coronary heart disease (CHD) mortality among RTRs. This retrospective study consists of 93,857 non-smoking adults who received a renal transplant between 2001 and 2015. Time-dependent Cox regression was used to assess the association between annual concentrations of PM2.5 and mortality risk. In the multivariable-adjusted models, a 10 μg/m3 increase in ambient PM2.5 levels found increased risk of all-cause (HR = 3.45, 95% CI: 3.08–3.78), CVD (HR = 2.38, 95% CI: 1.94–2.92), and CHD mortality (HR = 3.10, 95% CI: 1.96–4.90). Black recipients had higher risks of all-cause (HR = 4.09, 95% CI: 3.43–4.88) and CHD mortality (HR = 6.73, 95% CI: 2.96–15.32). High levels of ambient PM2.5 were associated with all-cause, CVD, and CHD mortality. The association tended to be higher among Black recipients than non-Blacks.

Thirdhand smoke associations with the gut microbiomes of infants admitted to a neonatal intensive care unit: An observational study

IntroductionMicrobiome differences have been found in adults who smoke cigarettes compared to non-smoking adults, but the impact of thirdhand smoke (THS; post-combustion tobacco residue) on hospitalized infants’ rapidly developing gut microbiomes is unexplored. Our aim was to explore gut microbiome differences in infants admitted to a neonatal ICU (NICU) with varying THS-related exposure. MethodsForty-three mother-infant dyads (household member[s] smoke cigarettes, n = 32; no household smoking, n = 11) consented to a carbon monoxide-breath sample, bedside furniture nicotine wipes, infant-urine samples (for cotinine [nicotine's primary metabolite] assays), and stool collection (for 16S rRNA V4 gene sequencing). Negative binomial regression modeled relative abundances of 8 bacterial genera with THS exposure-related variables (i.e., household cigarette use, surface nicotine, and infant urine cotinine), controlling for gestational age, postnatal age, antibiotic use, and breastmilk feeding. Microbiome-diversity outcomes were modeled similarly. Bayesian posterior probabilities (PP) ≥75.0% were considered meaningful. ResultsA majority of infants (78%) were born pre-term. Infants from non-smoking homes and/or with lower NICU-furniture surface nicotine had greater microbiome alpha-diversity compared to infants from smoking households (PP ≥ 75.0%). Associations (with PP ≥ 75.0%) of selected bacterial genera with urine cotinine, surface nicotine, and/or household cigarette use were evidenced for 7 (of 8) modeled genera. For example, lower Bifidobacterium relative abundance associated with greater furniture nicotine (IRR<0.01 [<0.01, 64.02]; PP = 87.1%), urine cotinine (IRR = 0.08 [<0.01,2.84]; PP = 86.9%), and household smoking (IRR<0.01 [<0.01, 7.38]; PP = 96.0%; FDR p < 0.05). ConclusionsTHS-related exposure was associated with microbiome differences in NICU-admitted infants. Additional research on effects of tobacco-related exposures on healthy infant gut-microbiome development is warranted.

Smoke-Free Laws and Disparities in Secondhand Smoke Exposure Among Nonsmoking Adults in the United States, 1999-2014.

Little is known about the relationship between smoke-free laws and persistent disparities in secondhand smoke (SHS) exposure among nonsmoking adults in the United States. We constructed time-varying smoke-free law measures representing whether or not at least 50% of each US county's population was covered by smoke-free laws in workplaces and hospitality venues (restaurants/bars). We merged these data with restricted data on cotinine-derived SHS exposure among nonsmokers from the National Health and Nutrition Examination Survey, 1999-2014 (N = 25 444). Using logistic regression, we estimated associations between smoke-free law coverage and SHS exposure among all nonsmokers, and within age strata (25-39, 40-59, 60+). We explored differential associations by gender, race/ethnicity, education, and poverty-income ratio (PIR) by testing the significance of interactions terms for the full sample and within age strata. In adjusted models, hospitality coverage was associated with lower odds of SHS exposure in the full sample (odds ratio [OR] = 0.62; 95% confidence interval [CI] = 0.51-0.76), and within each age group, with ORs ranging from 0.58 (ages 25-39) to 0.67 (ages 60+). Workplace coverage was associated with lower SHS exposure only among younger adults (OR = 0.81; 95% CI = 0.65-0.99). Within the full sample and among adults ages 40-59, hospitality laws were associated with narrowing SHS exposure differentials between males and females. Among adults ages 40-59, workplace laws were associated with narrowing exposure differentials between males and females, but worsening exposure disparities by PIR. Smoke-free laws may reduce SHS exposure among adult nonsmokers, but may be insufficient to improve disparities in SHS exposure. In a repeated cross-sectional sample of adult nonsmokers, smoke-free laws in hospitality venues were consistently associated with lower odds of SHS exposure and appeared to narrow exposure differentials between males and females. Associations between workplace smoke-free laws and SHS exposure were variable by age. Among adults ages 40-59, workplace laws were associated with narrowing exposure differentials between males and females while exacerbating exposure differentials by PIR. Differential patterns of association highlight the need to examine the impacts of tobacco control policies on downstream health equity.

Influence of CYP2C9, VKORC1, and CYP4F2 polymorphisms on the pharmacodynamic parameters of warfarin: a cross-sectional study.

Warfarin is the most commonly evaluated drug in pharmacogenetic-guided dosing studies. However, gaps remain regarding the influence of the genetic polymorphisms of CYP2C9, VKORC1, and CYP4F2 on specific pharmacodynamic parameters like the warfarin sensitivity index (WSI), prothrombin time international normalized ratio (PT-INR), and log-INR variability. A cross-sectional study was conducted in non-smoking adults receiving warfarin for at least 6months. Their demographics, diagnoses, warfarin dosing regimen, concomitant drugs, PT-INR, and bleeding episodes were obtained. CYP2C9 (rs1057910-*3 and rs1799853-*2 alleles), CYP4F2 (rs2108622), and VKORC1 (rs9923231) polymorphisms were assessed using real-time polymerase chain reaction. Three genotype groups (I-III) were defined based on the combined genetic polymorphisms of CYP2C9 and VKORC1 from the FDA's recommendations. Key outcome measures included anticoagulation control, time spent in therapeutic range, stable warfarin dose, WSI, log-INR variability, and Warfarin Composite Measure (WCM). The study recruited 236 patients; 75 (31.8%) carried a functional CYP2C9 variant allele, and, 143 (60.6%) had at least one T allele in CYP4F2 and 133 (56.4%) had at least one T allelein VKORC1. Groups' II and III CYP2C9 and VKORC1 genotypes were observed with reduced stable warfarin dose, increased WSI, higher log-INR variability, and increased bleeding risk. The presence of *2 or *3 allele in CYP2C9 was observed with reduced stable warfarin doses akin to the presence of T alleles in VKORC1; however, the doses increased with T alleles in CYP4F2. The evaluated genetic polymorphisms significantly influenced all the pharmacodynamic parameters of warfarin. Evaluating CYP2C9, VKORC1, and CYP4F2 genetic polymorphisms prior to warfarin initiation is likely to optimize therapeutic response.

Occupational Exposure to Second-Hand Tobacco Smoke: Development of a Job Exposure Matrix.

Exposure to second-hand tobacco smoke (SHS) in the workplace has been largely controlled in most workplaces in many countries that have adopted smoke-free laws and regulations. Workers in offices, bars, restaurants, and many other settings have experienced substantial reductions in the frequency and intensity of their exposure to SHS. While current exposure to SHS of most non-smoking adults arises from living with a smoker there are likely to be some jobs where non-negligible exposure to SHS continues to occur. This study describes the development of a simple job exposure matrix (JEM) for SHS exposure for the UK working population in 2020 and identifies that at least 1.04 million workers are likely to be exposed to SHS while performing their job. Occupations with the highest frequency and intensity of exposure include those where workers carry out work tasks in private, domestic settings: including care workers and home carers. This SHS-JEM provides a novel method for assessing occupational exposure to SHS in other countries, and can act as a tool to identify priorities for policies to protect those workers who continue to be at risk from SHS.

Atherosclerosis inflammation and burden in young adult smokers and vapers measured by PET/MR

Background and aimsElectronic cigarette (EC) use is popular among youth, touted as a safer alternative to smoking and promoted as a tool to aid in smoking cessation. EC cardiovascular safety however is not well established. The aim of this study was to examine cardiovascular consequences of EC use by evaluating their effect on the entire atherosclerotic cascade in young adults using noninvasive combined positron emission tomography (PET)/magnetic resonance imaging (MR) and comparing EC use with age matched smokers of traditional cigarettes and nonsmoking controls. MethodsCarotid PET/MR was applied to look at vascular inflammation (18-fluorodeoxyglucose (FDG)-PET) and plaque burden (multi-contrast MR of vessel wall) from 60 18-30 year-old subjects (20 electronic cigarette users, 20 traditional smokers and 20 nonsmokers). ResultsGroups were reasonably well balanced in terms of age, gender, demographics, cardiovascular risk and most biomarkers. There were no differences in vascular inflammation as measured by 18-FDG-PET target to background ratios (TBR) between EC users, traditional cigarette smokers and nonsmokers. However, measures of carotid plaque burden − wall area, normalized wall index, and wall thickness − measured from MR were significantly higher in both traditional smokers and EC users than in nonsmokers. ConclusionsYoung adult EC users, smokers and nonsmokers in our study did not exhibit vascular inflammation as defined by 18-F-FDG-PET TBR max, but smokers and EC users had significantly more carotid plaque burden compared to matched nonsmokers. Results could indicate that vaping does not cause an increase in vascular inflammation as measured by FDG-PET.

Trends in the Socioeconomic Inequalities Related to Second-Hand Smoke Exposure as Verified by Urine Cotinine Levels Among Nonsmoking Adults: Korea National Health and Nutrition Examination Survey 2008-2018.

The expansion of smoke-free policies has reduced the prevalence of second-hand smoke (SHS) exposure; however, declines differ according to socioeconomic positions. We evaluated the trends in socioeconomic inequalities related to SHS exposure in nonsmoking Korean adults from 2008 to 2018. We analyzed 30,027 nonsmoking adults from the Korea National Health and Nutrition Examination Survey 2008 to 2018. We evaluated trends in urine cotinine levels, self-reported prevalence of SHS exposure at workplaces and homes, and people exhibiting nonmeasurable urine cotinine levels between 2008 and 2018. To evaluate the yearly decline differences of urine cotinine levels according to socioeconomic positions, we calculated the interaction effects of year and education, household incomes, and occupation from linear regression analysis. In the last 11 years, the geometric means of urine cotinine levels decreased from 3.53 (95% CI 2.96-4.19) ng/mL to 0.60 (0.57-0.64) ng/mL in males, and from 2.36 (2.03-2.73) ng/mL to 0.53 (0.51-0.56) ng/mL in females. The prevalence of SHS exposure at workplaces and homes also declined. In the multivariate model, the interaction effects between education and years were significant; therefore, indicating a substantial yearly decline of urine cotinine levels in higher educated individuals. The interaction effects between household incomes and years were only significant among males; the interaction effects between occupations and years were not significant. SHS exposure in nonsmoking Korean adults has consistently decreased; however, socioeconomic inequalities related to SHS exposure by education level have widened. Policies targeting socioeconomically disadvantaged populations should be implemented to decrease the disparities of SHS exposure. Along with tobacco control policies, the prevalence of self-reported and urinary cotinine verified SHS exposure has decreased in the last 11 years. In contrast, the socioeconomic inequalities related to SHS exposure by education level have increased over time. This study emphasizes the need for implementing tobacco control policies to reduce disparities of SHS exposure.

‘95% less harmful’? Exploring reactions to quantitative modified risk claims for snus and e-cigarettes

ObjectivesStudies examining perceptions of ‘modified risk tobacco product’ (MRTP) messages for e-cigarettes and smokeless tobacco have indicated consumers want statistics and quantification of harm reduction. However, limited research exists on...

Variability of Urinary Creatinine in Healthy Individuals.

Many urinary biomarkers are adjusted for dilution using creatinine or specific gravity. The aim was to evaluate the variability of creatinine excretion, in 24 h and spot samples, and to describe an openly available variability biobank. Urine and blood samples were collected from 60 healthy non-smoking adults, 29 men and 31 women. All urine was collected at six time points during two 24 h periods. Blood samples were also collected twice and stored frozen. Analyses of creatinine in urine was performed in fresh urine using an enzymatic method. For creatinine in urine, the intra-class correlation (ICC) was calculated for 24 h urine and spot samples. Diurnal variability was examined, as well as association with urinary flow rate. The creatinine excretion rate was lowest in overnight samples and relatively constant in the other five samples. The creatinine excretion rate in each individual was positively correlated with urinary flow rate. The creatinine concentration was highest in the overnight sample and at 09:30. For 24 h samples the ICC was 0.64, for overnight samples it was 0.5, and for all spot samples, it was much lower. The ICC for urinary creatinine depends on the time of day of sampling. Frozen samples from this variability biobank are open for researchers examining normal variability of their favorite biomarker(s).

Effects of modified risk tobacco product claims on consumer comprehension and risk perceptions of IQOS

IntroductionTobacco industry studies on consumers’ perceptions of modified risk claims (MRCs) often had important omissions (eg, no control group, not investigating whether consumers understand what ‘switching completely’ means). This study...

QuickStats: Trends in Secondhand Smoke Exposure* Among Nonsmoking Adults, by Race† and Hispanic Origin - National Health and Nutrition Examination Survey, United States, 2009-2018.

QuickStats: Trends in Secondhand Smoke Exposure* Among Nonsmoking Adults, by Race† and Hispanic Origin - National Health and Nutrition Examination Survey, United States, 2009-2018.