Smokeless Tobacco Users Research Articles

Variability in addictive and carcinogenic potential of smokeless tobacco products marketed in Mumbai, India: a surveillance study

India has the highest incidence worldwide of smokeless tobacco (SLT)-associated oral cancer, accounting for nearly 70% of all SLT users globally. Nicotine and tobacco-specific N-nitrosamines (TSNA) play critical roles in the addictive and carcinogenic potential, respectively, of SLT products. Our group has previously reported substantial variability in nicotine and TSNA levels across a small SLT product sample in India, calling for systematic surveillance. However, there is no information available on the current levels of these constituents in Indian SLT. We analysed 321 samples representing 57 brands of eight popular types of manufactured SLT products purchased from five local markets in Mumbai, India between August, and September 2019. The sampling locations were Mumbai Central, Kurla, Thane, Vashi, and Airoli. Product pH, moisture content, total and unprotonated (biologically available) nicotine, and TSNA levels were measured at the Advanced Centre for Treatment, Research, and Education in Cancer (ACTREC) in Mumbai. Total nicotine content ranged from 0.45 to 35.1mg/g across products. The unprotonated nicotine fraction contributed 0.1-100% of the total nicotine content. The carcinogenic TSNA levels ranged 0.06-76 ug/g for N'-nitrosonornicotine (NNN), 0.02-19.2 ug/g for 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and 0.01-6.51 ug/g for 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL). Consistent with our previous study, we observed substantial variations across different brands of the same product type. This is the most extensive and the first within-country study to report brand-specific nicotine and TSNA levels in SLT products marketed in Mumbai, India. Our results show that levels of these constituents remain extremely variable across Indian SLT and are strikingly high in many products. Enhanced public education and continued efforts to reduce SLT use prevalence in India are critical for reducing the global burden of SLT-associated morbidity and mortality. Regulation of nicotine and TSNA levels in SLT products should be considered. This work was supported by the National Institutes of Health (USA) grant R01-TW010651 and, in part, by grants R01-CA180880 and R50-CA211256. The LC-MS/MS analysis was supported in part by XII Plan project funding from the Department of Atomic Energy, Government of India.

Abstract A092: Tobacco use and prevalence of oral premalignant lesions, among Malayali tribes, Yelagiri Hills, Tamil nadu, India

Abstract BACKGROUND: India has the second largest tribal population of the world next to the African countries. About half of the world’s autochthonous people live in India, thus making India home to many tribes which have an interesting and varied history of origins, customs and social practices. The present study was conducted to assess the tobacco use and prevalence of precancerous lesions and oral cancer among Malayali tribes, Yelagiri Hills, Tamil nadu, India. METHODOLOGY The inhabitants of the 14 villages of the Yelagiri hills, who have completed 18years and residing for more than 15years present on the day of examination and who were willing to participate in the study were included. Data was collected from a cross-sectional survey, using a Survey Proforma, clinical examination and a pre-tested questionnaire. An intra-oral examination was carried out by a single examiner using WHO Oral Health Surveys – Basic Methods Proforma (1997). ResultsThe overall prevalence of smokeless and smoking tobacco was 78.8% and 65.2% respectively among 1550 study population. Of those who had the habit of smoking, 26% smoked beedi, 10.9% smoked cigarette, 65% chewed raw tobacco, 18% chewed Hans and 28% had a combination of smoking and smokeless tobacco usage. Around 49.8% of samples were stained positive for precancerous and cancerous lesions of the oral cavity. The highest number of positive samples were from buccal mucosa with 46.2% subjects and 12% for labial mucosa. The reason for practicing these habits were as a measure to combat the cold, relieving stress and body pain after work, and the lack of awareness of the hazards of the materials used. Prevalence of oral mucosal lesions in the study population was due to tobacco usage and alcohol consumption and lack of awareness regarding the deleterious effects of the products used. CONCLUSION Oral cancer is highly prevalent in this Malayali tribes owing to high tobacco consumption rates and habits warranting the cessation center a priority. Also, early detection and screening are vital to attaining better outcomes. Citation Format: Delfin Lovelina Francis. Tobacco use and prevalence of oral premalignant lesions, among Malayali tribes, Yelagiri Hills, Tamil nadu, India [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A092.

Noticing health warning labels and intentions to quit smokeless tobacco products: results from two Global Adult Tobacco Survey rounds, India

Introduction: Health warning labels (HWLs) are one of the key strategies for tobacco control. The current study assessed the individual characteristics affecting the noticeability of HWLs and the thought of quitting smokeless tobacco (SLT) on noticing HWLs. We further estimated the temporal changes in noticeability and thought of quitting after noticing HWLs over time in India. Methods: Data from two rounds (2009–2010 and 2016–2017) of GATS (Global Adult Tobacco Survey) from India were analysed to understand the pattern of SLT usage and estimate the relative changes in the noticeability of HWLs and the thought of quitting SLT among those who noticed HWLs. Sampling weights were used during the analysis. Multivariate binary logistic regression was used to explore the determinants for the noticeability of HWLs and encourage the intention to quit SLT after noticing the HWLs. Results: About 25.9% and 20.6% of participants consumed SLT daily or non-daily in two rounds of GATS. Overall, there was a 14% relative increase in noticing the HWLs and a 20% increase in the thought of quitting in GATS-2 compared with GATS-1. The adjusted odds ratio of observing HWLs among SLT users was 1.51 times (95% confidence interval (CI), 1.44–1.58) in round 2 compared with round 1, while the odds ratio concerning the thought of quitting SLT after noticing HWLs was 1.95 times (95% CI, 1.84–2.06) in round 2 compared with round 1. Conclusions: We observe a consistent increase in the noticeability of HWLs and intentions to quit in SLT users, with significant variations across socio-demographic characteristics calling for concerted efforts. SLT being the major form of tobacco usage in India and Asian countries, HWLs alone cannot bring down the consumption rates, and it needs to be supported by strict implementation of SLT legislation for long-lasting impact.

Comparative Evaluation of Salivary Cathelicidin and 8-Isoprostane Levels Among Smokeless Tobacco Users and Non-users and Their Correlation With Periodontal Health and Disease: A Cross-Sectional Study

Comparative Evaluation of Salivary Cathelicidin and 8-Isoprostane Levels Among Smokeless Tobacco Users and Non-users and Their Correlation With Periodontal Health and Disease: A Cross-Sectional Study

Comparative proteomic analysis of saliva from chewing tobacco users and oral cancer patients reveals shared biomarkers: A case control observational study

ObjectiveThe aim of this study was to compare the salivary proteomic profile of smokeless tobacco users with that of non-users and oral cancer patients using Liquid Chromatography-Mass Spectrometry/ Mass Spectrometry (LC-MS/MS). MethodsSaliva samples from 65 participants were collected in three groups: control (25 participants), smokeless tobacco users (25 participants), and oral cancer (15 participants). ResultsThe analysis revealed 343 protein groups with significantly altered abundance in the saliva samples (P < 0.05). Among these, 43 out of 51 dysregulated proteins in the smokeless tobacco group were also dysregulated in the oral cancer group. Notably, Apolipoprotein A1 (ApoA1) and Pon1 were found to be significantly increased in both smokeless tobacco users and oral cancer patients (p < 0.05). Furthermore, six out of the 20 most significantly altered proteins were mitochondrial proteins, and all of these were decreased relative to controls in both smokeless tobacco users and cancer samples. ConclusionThe proteomic profile of users of chewing (smokeless) tobacco (SLT) shows substantial overlap in the altered pathways and dysregulated proteins with those altered in oral cancer samples, suggesting that SLT use induces a shift toward an oncogenic state. Specifically indicated pathways included blood microparticles, platelet α-granules and protease inhibitors as well as indicators of oxidative stress and exogenous compound processing. What differentiates oral cancer samples from SLT users is enrichment of alterations related to cytoskeletal organisation and tissue remodelling. Clinical SignificanceThe findings emphasize the importance of salivary proteomic profiles because changes in certain proteins may be indicators for early oral cancer identification and risk assessment in smokeless tobacco users.

Perspectives of smokers, smokeless tobacco users and cessation practitioners in India: A qualitative study

IntroductionIndia is the second largest consumer of tobacco in the world and accounts for 70% of global deaths due to smokeless tobacco (SLT) use. AIM: The aim of this study is to understand the perspectives of tobacco users (smokers and SLT users) and practitioners in India to inform cessation interventions. MethodSemi-structured in-depth interviews with tobacco users (smoked and smokeless; n=23), and healthcare practitioners (n=13). Perspectives were triangulated using thematic analysis to examine convergence, divergence and complementarity of findings. ResultsWe present the results in a socio-ecological framework to highlight reasons for initiation and continuation of tobacco and motives to quit at the individual, interpersonal, occupational, societal and policy levels. SLT is seen as culturally acceptable compared to smoked forms of tobacco. Emotionally framed messages highlighting negative effects of tobacco on loved ones were perceived to be a better motivator than other types of cessation messages. DiscussionNuanced differences exist between smokers and SLT user perspectives which have implications for cessation programs. Our findings supplement similar studies with other South Asian populations. Implications for PracticeOur study provides useful insights to tailor cessation interventions to the type of tobacco consumed in order to enhance their acceptability and effectiveness.

Microbial community and functions involved in smokeless tobacco product: a metagenomic approach

Smokeless tobacco products (STPs) are attributed to oral cancer and oral pathologies in their users. STP-associated cancer induction is driven by carcinogenic compounds including tobacco-specific nitrosamines (TSNAs). The TSNAs synthesis could enhanced due to the metabolic activity (nitrate metabolism) of the microbial populations residing in STPs, but identifying microbial functions linked to the TSNAs synthesis remains unexplored. Here, we rendered the first report of shotgun metagenomic sequencing to comprehensively determine the genes of all microorganisms residing in the Indian STPs belonging to two commercial (Moist-snuff and Qiwam) and three loose (Mainpuri Kapoori, Dohra, and Gudakhu) STPs, specifically consumed in India. Further, the level of nicotine, TSNAs, mycotoxins, and toxic metals were determined to relate their presence with microbial activity. The microbial population majorly belongs to bacteria with three dominant phyla including Actinobacteria, Proteobacteria, and Firmicutes. Furthermore, the STP-linked microbiome displayed several functional genes associated with nitrogen metabolism and antibiotic resistance. The chemical analysis revealed that the Mainpuri Kapoori product contained a high concentration of ochratoxins-A whereas TSNAs and Zink (Zn) quantities were high in the Moist-snuff, Mainpuri Kapoori, and Gudakhu products. Hence, our observations will help in attributing the functional potential of STP-associated microbiome and in the implementation of cessation strategies against STPs.Key points•Smokeless tobacco contains microbes that can assist TSNA synthesis.•Antibiotic resistance genes present in smokeless tobacco-associated bacteria.•Pathogens in STPs can cause infections in smokeless tobacco users.

Trends in smokeless tobacco use and attributable mortality and morbidity in the South-East Asia Region: implications for policy

ObjectivesTo describe the prevalence of smokeless tobacco (SLT) use and number of users by year, in addition to trends in mortality and attributable disease burden in countries of the WHO...

Intention to Quit Tobacco due to Media Advertisements in India: Findings from Global Adult Tobacco Survey 2016-17.

Tobacco has been among the most important causes of morbidity and mortality worldwide. In reducing tobacco consumption, media campaigns are crucial in raising awareness and encouraging individuals to quit. The present study aimed to profile participants of GATS-2, including tobacco usage patterns and media exposure, and explore the factors associated with quitting in the presence of media exposure. Secondary data analysis of Global Adult Tobacco Survey-India (2016-17) data was done among current daily cigarette smokers and smokeless tobacco users. The primary independent variable was an intention to quit, while media exposure was the primary independent variable. Respondents were profiled as per various socio-demographic variables, and exposure to media advertisements and intention to quit were assessed using weighted bivariate analysis and multivariate log regression analysis. Males, and respondents aged 15 to 45, had more exposure to media and advertisements than female respondents. Cigarette smokers with moderate consumption, better awareness, those who had made any quit attempts in the last 12 months, and moderate to high media exposure depicted better intention to quit. In SLT users, intention to quit depicted significant odds per education level quit attempts and exposure to media and advertisements. We report a high intention to quit among those exposed to advertisements. Media campaigns play an important role in promoting tobacco control. There is a need to assess the impact of such advertisements on behavioral aspects. At the same time, comprehensive tobacco control policies should go hand in hand in reducing smoking rates.

Behavioural support and nicotine replacement therapy for smokeless tobacco cessation in Bangladesh, India and Pakistan: A pilot randomized controlled trial.

Smokeless tobacco (ST) use in South Asia is high, yet interventions to support its cessation are lacking. We tested the feasibility of delivering interventions for ST cessation in South Asia. We used a 2× 2 factorial design, pilot randomized controlled trial with a duration of 26 weeks, including baseline and follow-up (6, 12 and 26 weeks) assessments. Two primary health-care facilities each in Dhaka (Bangladesh) and Karachi (Pakistan) and a walk-in cancer screening clinic in Noida (India) took part. Adult daily ST users willing to make a quit attempt within 30 days. Of 392 screened, 264 participants [mean age: 35 years, standard deviation = 12.5, 140 (53%) male] were recruited between December 2020 and December 2021; 132 from Bangladesh, 44 from India and 88 from Pakistan. Participants were randomized to one of three treatment options [8-week support through nicotine replacement therapy (NRT, n= 66), a behavioural intervention for smokeless tobacco cessation in adults (BISCA, n= 66) or their combination (n= 66)] or the control condition of very brief advice (VBA) to quit (n= 66). Recruitment and retention, data completeness and feasibility of intervention delivery were evaluated. Biochemically verified abstinence from tobacco, using salivary cotinine, was measured at 26 weeks. Retention rates were 94.7% at 6 weeks, dropping to 89.4% at 26 weeks. Attendance in BISCA pre-quit (100%) and quit sessions (86.3%) was high, but lower in post-quit sessions (65.9%), with variability among countries. Adherence to NRT also varied (45.5% Bangladesh, 90% India). Data completion for key variables exceeded 93% among time-points, except at 26 weeks for questions on nicotine dependence (90%), urges (89%) and saliva samples (62.7%). Among follow-up time-points, self-reported abstinence was generally higher among participants receiving BISCA and/or NRT. At 26 weeks, biochemically verified abstinence was observed among 16 (12.1%) participants receiving BISCA and 13 (9.8%) participants receiving NRT. This multi-country pilot randomized controlled trial of tobacco cessation among adult smokeless tobacco users in South Asia demonstrated the ability to recruit and retain participants and report abstinence, suggesting that a future definitive smokeless tobacco cessation trial is viable.

Smokeless tobacco and periodontitis: A systematic review with meta-analysis.

The present systematic review with meta-analysis aimed to investigate the global association between smokeless tobacco (SLT) use and periodontitis, considering significant effect size variation based on the income levels of countries. We searched seven databases to identify studies that assessed the prevalence of periodontitis in adult SLT users compared to non-users. The quality of studies was evaluated using the 10-item risk-of-bias tool, and publication bias was addressed through the trim-and-fill method. Sensitivity analysis utilized the leave-one-out approach. Meta-analysis and meta-regression, stratified by country income, SLT type, and smoking status, employed robust variance estimation. From an initial pool of 484 studies, 29 studies met the selection criteria and were subjected to qualitative synthesis. Subsequently, data from 19 studies were included in the meta-analysis. SLT users exhibited a nearly threefold greater likelihood of periodontitis compared to non-users (OR = 2.99; 95% CI: 2.10, 4.27; p < .01). The pooled estimate did not vary significantly based on the type of SLT used or concurrent smoking. However, the odds of periodontitis varied according to the economic level of the country; the pooled estimate was higher in high-income countries (OR = 1.69; 95% CI: 1.20, 2.37; p < .01) and even higher in lower-middle-income and lower-income countries (OR = 3.91; 95% CI: 2.66, 5.77; p < .01). Smokeless tobacco users have a higher likelihood of developing periodontitis. This study underscores global disparities in the SLT-periodontitis relationship, highlighting the need for targeted interventions, particularly in economically challenged areas where SLT use is largely unregulated.

Process evaluation of a pragmatic feasibility trial on smokeless tobacco cessation intervention delivered in dental hospitals

BackgroundArticle 14 of the WHO ‘Framework Convention on Tobacco Control’ recommends, that all oral healthcare providers provide support for tobacco cessation, to all patients. Despite evidence on the effectiveness of tobacco cessation interventions in dental settings, implementation remains low in most high-burden countries like Pakistan. A pragmatic pilot trial of a dentist-delivered behavioural support intervention for smokeless tobacco (ST) cessation, was conducted in dental hospitals in Pakistan. This paper presents the findings of the process evaluation of the trial.MethodsA mixed-method process evaluation of a multi-centre randomised control pilot trial of dentist-delivered behavioural support intervention ST cessation was conducted. The intervention included three sessions namely: pre-quit, quit and post-quit sessions. The process evaluation involved: semi-structured interviews with trial participants (n = 26, of which dental patients were n = 13 and participating dentists were n = 13 conducted from June-August 2022); and fidelity assessment of audio recordings of the intervention sessions (n = 29). The framework approach was used to thematically analyse the interview data.ResultsOverall the trial procedures were well accepted, however, young patients expressed uneasiness over revealing their ST use status. The intervention was received positively by dentists and patients. Dentists identified some challenges in delivering behavioural support to their patients. Of these, some were related to the contents of the intervention whereas, others were related to the logistics of delivering the intervention in a clinical setting (such as workload and space). Acceptability of the intervention resources was overall low amongst young patients as they did not take the intervention resources home due to fear of their family members finding out about their ST use. The intervention was successful in achieving the intended impact (in those who engaged with the intervention), i.e., change in the patients’ ST use behaviour. Giving up ST with the aid of behavioural support also had an unintended negative effect i.e., the use of harmful substances (cannabis, cigarettes) to give up ST use. Patients’ satisfaction with their dental treatment seemed to influence the intervention outcome.ConclusionWhile there are many variables to consider, but for the participants of this study, behavioural support for abstinence delivered through dentists during routine dental care, appears to be an acceptable and practical approach in helping patients give up ST use, in a country like Pakistan, where negligible support is offered to ST users.

Effects of Smokeless Tobacco on Oral Health: A Cross-Sectional Study.

Smokeless tobacco (SLT) consumption poses a significant global public health challenge because of its adverse effects on oral health. Although the detrimental impact of SLT on oral tissues is well-documented, understanding its multifaceted effects is essential for effective prevention and intervention strategies. This study aimed to comprehensively assess the impact of SLT on oral health, focusing on various clinical parameters and their differences between placement and non-placement sites of SLT. A cross-sectional study involving 528 habitual users of SLT was conducted. Clinical parameters included the plaque index (PI), gingival index (GI), gingival bleeding index (GBI), gingival recession (GR), and probing depth (PD). Oral mucosal changes at SLT placement sites have also been reported. Statistical analysis was performed to compare parameters between the placement and non-placement sites. The study involved 528 subjects, mostly male (82%) and aged 21-40 years (mean±SD=31.14±9.10), habitual users of SLT. Prevalent SLT types included tobacco with betel nuts/masala/gutkha (59.9%) and tobacco with lime (54.5%). Significant differences were observed between SLT placement and non-placement sites: higher gingival inflammation (GI) at placement sites (1.54±0.61 vs. 1.45±0.54, p=0.01), lower GBI at placement sites (40.0% vs. 84.3%, p=0.001), and more prevalent GR (65.7% vs. 34.3%, p=0.03) at placement sites. Probing depths ≥ 3 mm were also less frequent at placement sites (2.67±0.72) than non-placement sites (3.37±1.03, p=0.001). These results highlight the detrimental impact of SLT on periodontal health, emphasizing the need for targeted interventions among SLT users. SLT use is associated with adverse effects on oral health, including GI, plaque accumulation, gingival bleeding, GR, and changes in the oral mucosa. Targeted interventions and public health policies are needed to address these issues effectively.

A Study On Insight Into Cessation Attempts Among Current Smokeless Tobacco Users In An Urban Slum Of Ahmedabad

Introduction:According to GATS-2 report, one out of every five persons in Gujarat uses smokelesstobacco (SLT).Tobacco causes addiction &amp; dependence over a period of time.Tobacco cessation is anintegral part of the National Tobacco Control Programme.Objective:To estimate the proportion ofprevious quit attempts and its determinants among current SLT users of an urban slum inAhmedabad.Methods:A community-based, cross-sectional study using consecutive sampling wasconducted between June 2023 - August 2023 among 250 current SLT users in an urban slum ofAhmedabad( Ward number 15). A pre-tested, semi-structured questionnaire adapted from GATS-2(Global Adult Tobacco Survey-2) Tobacco Questions for Surveys was administered among theparticipants for eliciting sociodemographic characteristics, SLT consumption pattern and quittingattempts. Results:In this study, 68.8% of the participants had at least one past quit attempt out ofwhich 94.7% tried self- control methods. The most common reason for not being able to quit wasperceived as addiction (70.9%). A larger part of SLT users (89%) had noticed warning labels intobacco packets and 18.3% of them reported that they thought of quitting seeing that warning. Threefourth of the participants were advised by at least one person to not consume tobacco products &amp; in60% of the cases, it was the spouse.Conclusions and recommendations:The results suggest that there is an obvious lacuna in the community's utilization of services, despite the fact that National Tobacco Control Programme (NTCP) provides nationwide cessation services. This demonstrates theneed for extensive community-based tobacco cessation activities. Keywords:Smokelesstobacco(SLT), Addiction,Quit Attempt, National Tobacco Control Programme(NTCP)

The Lifetime Health and Economic Burden of Smokeless Tobacco use in Bangladesh, India, and Pakistan: Results From ASTRAMOD.

Under the current policy landscapes, the lifetime health and economic burden of smokeless tobacco (ST) products, consumed by over 297 million ST users in South Asia, is unknown. The aim of this study was to estimate the lifetime health effects and costs attributable to current and future ST use in Bangladesh, India, and Pakistan where the majority of ST users live. We developed a Markov-based state-transition model (ASTRAMOD) to predict the lifetime costs of treatment of four diseases (oral, pharyngeal, esophageal cancers, and stroke) and disability-adjusted life years (DALYs), attributable to the current and future use of ST under existing ST policy scenario. Country-specific Global Adult Tobacco Surveys, life tables, and meta-analyses of South Asian and South East Asian studies were used to populate the model. A probabilistic sensitivity analysis evaluated the uncertainty in model predictions. If there were no change in the current ST policies, the lifetime ST-attributable treatment costs would be over US$19 billion in India, over US$1.5 billion in Bangladesh, and over US$3 billion in Pakistan. For all countries, the attributable costs are higher for younger cohorts with costs declining with increasing age for those over 50. The model predicted that a typical 15-year-old male adoloscent would gain 0.07-0.18 life years, avert 0.07-0.19 DALYs, and generate a cost-savings of US$7-21 on healthcare spending if ST policies were changed to eliminate ST use. Policy interventions aimed at decreasing the uptake of ST and increasing quitting success have the potential to substantially decrease the economic and health burden of ST. This study provides the most comprehensive estimates of the lifetime health and economic burden of ST by 5-year age and sex cohorts. This is also the first study that highlights the scale of health and economic burden of ST in Bangladesh, India, and Pakistan if there were no changes in the current ST policies. Policymakers and practitioners can use the reported data to justify their decisions to improve current ST policies and practices in their country. Researchers can use the ASTRAMOD methodology to estimate the impact of future ST policy changes.

Investigating the discriminatory potential of urinary DNA adductomics in smokeless tobacco-treated rats and head-neck cancer patients

The genotoxicity of smokeless tobacco (ST) remains an essential public health issue. We conducted a comprehensive study of rats exposed to ST and head and neck cancer patients to elucidate the DNA adduct profiles. ST exposure assessment used alkaloids and tobacco-specific nitrosamines in rat urine. High ST doses led to significantly elevated nicotine, cotinine, N-nitrosonornicotine (NNN), and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) levels, indicating substantial exposure. DNA adductomics identified 17 significant DNA adducts using a neutral loss scan in liquid chromatography-mass spectrometry in rat urine samples upon ST exposure, highlighting the intricate landscape of DNA modifications associated with ST using univariate and multivariate statistical analyses. LC-ESI-QTOF-MS/MS analysis and accurate mass measurements of DNA adducts unveiled specific adducts upregulated in response to ST exposure, particularly those associated with methylation and NNK release. Intriguing correlations emerged between DNA adducts and alkaloids-TSNA in ST-exposed rat urine. Nicotine correlated positively with N2-paraldol-dG and O2/O4-[4-(3-Pyridyl)-4-oxobut-1-yl] thymidine in high-dose rats. NNK correlated with 6O-methylgaunine, while NNN correlated with 6-hydroxy-1-N2-propanodeoxyguanosine and 7-methylguanine. With this aim, we also applied analysis to human samples, where we observed specific DNA adducts for ST users, controls, and subjects with HNC. Two-way ANOVA showed that ST users and cancer patients had higher DNA adduct levels in human urine, which aids cancer risk assessment, early detection, and environmental exposure evaluation. This comprehensive study explores DNA adducts caused by ST exposure across rats and head and neck cancer patients, illuminating genotoxic mechanisms and health risks and providing valuable insights for future preventive and therapeutic strategies.

Oral microbiome dysbiosis among cigarette smokers and smokeless tobacco users compared to non-users

Tobacco use significantly influences the oral microbiome. However, less is known about how different tobacco products specifically impact the oral microbiome over time. To address this knowledge gap, we characterized the oral microbiome of cigarette users, smokeless tobacco users, and non-users over 4 months (four time points). Buccal swab and saliva samples (n = 611) were collected from 85 participants. DNA was extracted from all samples and sequencing was carried out on an Illumina MiSeq, targeting the V3–V4 region of the 16S rRNA gene. Cigarette and smokeless tobacco users had more diverse oral bacterial communities, including a higher relative abundance of Firmicutes and a lower relative abundance of Proteobacteria, when compared to non-users. Non-users had a higher relative abundance of Actinomyces, Granulicatella, Haemophilus, Neisseria, Oribacterium, Prevotella, Pseudomonas, Rothia, and Veillonella in buccal swab samples, compared to tobacco users. While the most abundant bacterial genera were relatively constant over time, some species demonstrated significant shifts in relative abundance between the first and last time points. In addition, some opportunistic pathogens were detected among tobacco users including Neisseria subflava, Bulleidia moorei and Porphyromonas endodontalis. Overall, our results provide a more holistic understanding of the structure of oral bacterial communities in tobacco users compared to non-users.

Impact of Smokeless Tobacco on Cardiovascular Disease Risk in a Nigerian Metropolitan City.

The use of smokeless tobacco products (STP) as a substitute for tobacco smoking is driving increasing consumption of these products especially in developing countries. The study sought to make comparison of cardiovascular risk profile between chronic STP users and suitably matched tobacco-naïve controls. This is a preliminary report from the cross sectional part of a two-arm prospective study of Smokeless Tobacco Products Composition and Exposure Outcome in Enugu metropolis, Nigeria. Consecutively recruited current Smokeless tobacco users, who had no history of cigarette smoking, aged 18years and above, residing in selected communities in Enugu metropolis, Nigeria were recruited for the study from October 2022 to July 2023. Age and sex matched non-tobacco users from same localities as the study subjects served as controls. Written informed consent to participate in the study was obtained from all study participants. All participants were screened by the investigators, using the study case report forms, to obtain data on medical history, demographic, clinical, laboratory, and electrocardiographic evaluation. Data from 54 STP-users and 54 non-STP-users (mean age 56.58 ± 8.15years) were analyzed. Anthropometric parameters were similar in both groups. Smokeless tobacco users had higher erect and supine blood pressure indices as well asgreater postural drop in systolic blood pressure. The occurrence of diabetes mellitus (20.37% versus 5.56%) and hypertension (25.93%; 11.11%) was significantly higher in the STP-users than in the non-user population, (p = 0.02192 and 0.04751 respectively). Electrocardiographic evaluation showed significantly increased QTc and dispersions of P-wave, QRS and QT intervals as well as reduced PR interval in STP users. Electrocardiographic abnormalities observed in STP users include left ventricular hypertrophy, left atrial enlargement, ST-segment elevation, short PR interval and long QTc. Use of smokeless tobacco products is associated with increased risk burden of diabetes mellitus and hypertensive heart disease. Electrocardiographic findings linked to STP-use in this study are features consistent with arrhythmia, ventricular repolarization abnormality, myocardial hypertrophy and ischaemia, suggesting that smokeless tobacco products are not safe substitutes for tobacco smoking.

Feasibility randomised controlled trial of face-to-face counselling and mobile phone messages compared to usual care for smokeless tobacco cessation in Indian primary care: Project CERTAIN.

Smokeless tobacco (SLT) use in low- and middle-income countries (LMICs) has adverse health consequences. We hypothesize that it is feasible to test an intervention of mobile phone messages and face-to-face counselling session for SLT cessation in India. We conducted an exploratory, individual parallel two group, randomised controlled trial (RCT), with baseline -and end-point (three months from randomisation) assessments in urban primary health centres in Odisha, India. A total of 250 current (i.e., users in the last three months) SLT users or dual users (i.e., smokers and SLT users) were recruited to the trial (125 in each group). Participants were randomised to either routine care, face-to-face counselling, and reminder mobile messages or routine care only. The primary outcomes were to assess the feasibility of running a full RCT including recruitment, compliance, and retention. A total seven (77.8%) out of nine primary care centres took part in the trial. Out of the 315 SLT users invited to participate, 250 provided consent and were randomised [79.4% (95% CI: 74.5, 83.7)]. Out of the 250 randomised SLT users, 238 [95% (95% CI: 91.8, 97.5)] were followed up at three months (117 in the intervention group and 121 in the control group). Of the participants in the intervention group, 74 (63.8%) reported that they received the mobile messages. This exploratory trial demonstrated the feasibility of delivering and evaluating an intervention of mobile phone messages and face-to-face counselling for SLT users in Indian primary care in a full randomised trial. This study found that combining mobile messages with face-to-face counselling for smokeless tobacco users visiting primary health care settings in India is feasible in terms of recruitment of users, compliance with the intervention, and retention of study participants within the trial.The biochemically verified smokeless tobacco abstinence rate was higher in the intervention group compared with the control groupThere was poor agreement between self-reported tobacco cessation and the measured salivary cotinine in smokeless tobacco users.The findings support the feasibility and acceptability of the intervention signalling the need for a larger clinical trial to test effectiveness of the intervention.

Exploring the cessation efficacy and harm reduction potential of heated tobacco and nicotine pouch products in smokers and smokeless tobacco users: study protocol of a 6-month randomized controlled switching trial

Background: Despite decades of research on pharmacological and behavioural smoking cessation treatments, current quit aids are of limited success. The introduction of new, combustion-free nicotine and tobacco products extended the tool kit for people who smoke to switch away from their risky habit. We performed a systematic review including 120 studies resulting in several recommendations for a robust study design to determine the cessation efficacy of a new nicotine or tobacco product. Consequently, we prepared this study protocol to assess the cessation efficacy of heated tobacco products (HTPs) and nicotine pouches (NPs). Methods: 250 subjects (125 exclusive smokers and 125 exclusive smokeless tobacco (SLT) users) will be recruited and offered a choice of HTPs in case of smokers and a choice of NPs in case of SLT users in order to switch. Subjects will undergo four visits (baseline, 1, 3, and 6 months) to collect biospecimens and for physical examinations. Use behaviour and questionnaires will be monitored on a regular basis by means of a smartphone-app. We describe a sensitive and specific compliance monitoring using suitable biomarkers of exposure. The sample size of 250 subjects and duration of 6 months will allow the quit rates to be assessed with sufficient statistical power. Finally, the choice between different products shall reflect the individuals’ preferences. Conclusions: This protocol can be applied generically, providing a robust determination of a products’ cessation efficacy. Trial Registration: The trial will be registered in the International Clinical Trials Registry Platform.