Systematic review and meta-analyses of cytisine to support tobacco cessation.

BACKGROUND AND AIMS: Cytisine (also known as cytisinicline) is a low-cost partial agonist of nicotinic acetylcholine receptors used to assist tobacco cessation. We aimed to review the effectiveness of cytisine for tobacco cessation and the effects of dose and co-use of behavioural or other pharmacological interventions on cessation outcomes. METHODS: We searched seven databases, Google Scholar, and reference lists of included publications for randomised controlled trials investigating use of cytisine as a tobacco cessation aid. Studies were eligible if participants were ≥15 years old and used tobacco upon study enrolment. We conducted four random effects meta-analyses and sensitivity analyses with fixed effects models. We used the Cochrane risk-of-bias tool for randomised trials version 2 to assess risk of bias in included studies, with adjustments recommended by the Cochrane Tobacco Addiction Group. RESULTS: Participants using cytisine were significantly more likely to quit tobacco than participants who received placebo/no intervention/usual care (risk ratio [RR] = 2.65, 95% confidence interval [CI] = 1.50-4.67, 6 trials, 5194 participants) or nicotine replacement therapy (RR = 1.36, 95% CI = 1.06-1.73, p = 0.0152, 2 trials, 1511 participants). The difference in cessation rates among participants receiving cytisine versus varenicline was not statistically significant (RR = 0.96, 95% CI 0.63-1.45, P = 0.8464, 3 trials, 2508 participants). Two trials examined longer versus shorter treatment duration, finding higher abstinence rates with longer treatment (RR = 1.29, 95% CI = 1.02-1.63, 2 trials, 1009 participants). The differences in the number of adverse events reported by participants who received cytisine versus placebo (RR = 1.19, 95% CI = 0.99-1.41, P = 0.0624; 6 trials; 4578 participants) or cytisine versus varenicline (RR = 1.37, 95% CI = 0.57-3.33, P = 0.4835; 2 trials; 1345 participants) were not statistically significant. Most adverse events were mild (e.g. abnormal dreams, nausea, headaches). CONCLUSIONS: Cytisine is an effective aid for tobacco cessation and appears to be more effective for tobacco cessation than placebo, no intervention, usual care and nicotine replacement therapy.

The effect of tobacco tax increase on price-minimizing tobacco purchasing behaviours: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Tobacco product excise taxes are a cost-effective method for reducing tobacco consumption, but industry pricing and marketing strategies encourage consumers to engage in price-minimizing behaviours (PMBs). We investigated the relationship between tobacco tax increases and PMBs, measuring whether PMBs intensify following tax increases, whether low-income consumers with higher nicotine dependence are more likely to engage in PMBs and whether PMBs are negatively related to smoking cessation. METHOD: This was a systematic review with meta-analysis of cross-sectional and longitudinal studies from seven databases up to March 2023, using studies that reported any product- and purchasing-related smoking behaviours post-tobacco tax increase in a general representative population. Sixty-eight studies were quality-assessed using the Newcastle-Ottawa scale. All studies were narratively synthesized, with five studies involving 13 068-26 575 participants providing data for pooled analyses on PMBs [purchasing lower-priced brands, roll-your-own (RYO) tobacco and cartons] pre- and post-tax increases using a random effects meta-analytical model. RESULTS: Fifty-seven studies reported on legal PMBs, and 17 studies reported illicit cigarette purchasing. Meta-analysis showed that consecutive tax increases were positively associated with purchasing RYO [odds ratio (OR) = 1.60, 95% confidence interval (CI) = 1.04-2.46], especially in higher tobacco taxing environments, with substantial heterogeneity (I2 = 96%). Lower income and higher nicotine dependence were associated with purchasing lower-priced brands and RYO, whereas higher income and nicotine dependence were associated with purchasing cartons, large-sized packs and cross-border sales. Less evidence associated illicit tobacco purchases with tax increases or PMBs with smoking cessation. CONCLUSIONS: Tobacco purchasers' PMBs vary widely by state, country and time-period within countries. Both legal and illegal PMBs, potentially influenced by industry pricing tactics, may exacerbate health inequalities and dilute the public health benefits of tobacco tax increases.

Integrated Safety Update of Abrocitinib in 3802 Patients with Moderate-to-Severe Atopic Dermatitis: Data from More than 5200 Patient-Years with Up to 4 Years of Exposure.

BACKGROUND: Abrocitinib, an oral, once-daily, Janus kinase 1-selective inhibitor, is efficacious in moderate-to-severe atopic dermatitis with a manageable long-term safety profile. OBJECTIVE: We aimed to provide updated integrated long-term safety results for abrocitinib from available data accrued up to a maximum of almost 4 years in patients with moderate-to-severe atopic dermatitis from the JADE clinical development program. METHODS: Analysis included 3802 patients (exposure: 5213.9 patient-years) from the phase II monotherapy study (NCT02780167) and the phase III studies JADE MONO-1 (NCT03349060), JADE MONO-2 (NCT03575871), JADE TEEN (NCT03796676), JADE COMPARE (NCT03720470), JADE DARE (NCT04345367; 200 mg only), JADE REGIMEN (NCT03627767), and JADE EXTEND (NCT03422822; data cutoff 25 September, 2021). Data from patients receiving one or more doses of abrocitinib 200 mg or 100 mg were pooled in a consistent-dose cohort (patients were allocated to receive the same abrocitinib dose throughout exposure in the qualifying parent study and/or long-term study) or a variable-dose cohort (patients received open-label abrocitinib 200 mg; responders were randomized to abrocitinib 200 mg, 100 mg, or placebo, and could then receive abrocitinib 200 mg plus topical corticosteroids as rescue therapy). Incidence rates of adverse events of special interest were assessed. Cox regression analysis of risk factors for herpes zoster and serious infections was performed. RESULTS: Overall, this safety analysis of long-term data up to a maximum of ~ 4 years of abrocitinib exposure does not indicate any changes from the previously reported risk profile. The most frequent serious infections (per Medical Dictionary for Regulatory Activities preferred term) with consistent-dose abrocitinib 200 mg and 100 mg were herpes zoster (0.5% and 0.2%), pneumonia (0.2% with either dose), and herpes simplex (0.1% with either dose). Risk factors for herpes zoster were a history of herpes zoster, abrocitinib 200-mg dose, age ≥ 65 years, absolute lymphocyte count < 1 × 103/mm3 before the event, and residing in Asia. For serious infections, > 100 kg body weight was a risk factor. Incidence rate/100 patient-years (95% confidence interval) with the consistent abrocitinib 200-mg and 100-mg dose combined was higher in older (aged ≥ 65 years) patients versus younger (aged 18 to < 65 years) patients for serious adverse events (17.6 [11.7‒25.4] vs 6.7 [5.8‒7.8]), malignancy excluding non-melanoma skin cancer (2.4 [0.6‒6.0] vs 0.1 [0.0‒0.4]), non-melanoma skin cancer (2.4 [0.6‒6.1] vs 0.2 [0.1‒0.4]), lymphopenia (3.5 [1.3‒7.6] vs 0.1 [0.0‒0.3]), and venous thromboembolism (1.7 [0.4‒5.1] vs 0.1 [0.0‒0.3]). Incident rate/100 patient-years (95% confidence interval) of non-melanoma skin cancer with the consistent abrocitinib 200-mg and 100-mg dose combined was higher in current/former smokers (0.9 [0.4‒1.6]) vs never-smokers (0.0 [0.0‒0.1]). CONCLUSIONS: This safety update showed a consistent profile for abrocitinib with no new safety signals and continues to support that abrocitinib has a manageable long-term safety profile in patients with moderate-to-severe atopic dermatitis. Risk of specific adverse events was higher in certain patient populations, especially those aged ≥ 65 years. [Video abstract available.] CLINICAL TRIAL REGISTRATION: NCT02780167; study start date: April, 2016; primary completion date: March, 2017; study completion date: April, 2017. NCT03349060; study start date: 7 December, 2017; study completion date: 26 March, 2019. NCT03575871; study start date: 29 June, 2018; study completion date: 13 August, 2019. NCT03720470; study start date: 29 October, 2018; primary completion date: 27 December, 2019; study completion date: 6 March, 2020. NCT03796676; study start date: 18 February, 2019; study completion date: 8 April, 2020. NCT03627767; study start date: 11 June, 2018; primary completion date: 2 September, 2020; study completion date: 7 October, 2020. NCT04345367; study start date: 11 June, 2020; primary completion date: 16 December, 2020; study completion date: 13 July, 2021. NCT03422822; study start date: 8 March, 2018; study completion date: ongoing (estimated completion date: 31 January, 2026).

Abrocitinib is an approved treatment for people with moderate or severe atopic dermatitis, also known as AD or atopic eczema. Abrocitinib is a tablet that is taken by mouth once a day. This safety analysis looked at the side effects of treatment in a large group of adults and adolescents with moderate or severe AD who took abrocitinib up to a maximum of almost 4 years. This analysis also looked at which people were more likely to have certain side effects after taking abrocitinib. The results from this analysis were similar to those of previous safety analyses with abrocitinib, with no new side effects. Infections such as shingles, pneumonia, or herpes simplex can occur during treatment with abrocitinib. Shingles was more likely to occur in people who previously had shingles before taking abrocitinib, or who took the higher dose of abrocitinib (200 mg), or were 65 years of age or older, or had certain blood test results, or lived in Asia. People who are 65 years of age or older and took abrocitinib were more likely to develop some types of cancer, have certain abnormal blood test results, or develop blood clots in the veins than people with AD who were younger and took abrocitinib. Current or former smokers with AD who took abrocitinib were more likely to develop skin cancer (but not melanoma) than people with AD who took abrocitinib but have never smoked. This analysis further shows that abrocitinib had manageable safety in patients with moderate-to-severe AD. Video abstract: Integrated safety update of abrocitinib in 3802 patients with moderate-to-severe atopic dermatitis: data from more than 5200 patient-years with up to 4 years of exposure (MP4 63720 KB).

The underbelly of E-cigarette advertising: regulating online markets on social media platforms.

Australia prohibits the sale of nicotine-vaping products unless prescribed by medical practitioners. Significant policy reforms were announced on the 28th of November 2023 including a ban on single-use disposable vapes with and without nicotine, and the removal of the personal importation scheme. Despite stringent regulations, loopholes exist such that e-cigarette vendors are getting around it, and online markets provide a route to do so. We discuss strategies used by vendors to covertly market e-cigarettes online through social media. In this perspective, we highlight three proposed policies to strengthen social media regulations that may be feasible to implement. Our proposed strategies to regulate e-cigarette product listings on social media involve implementing robust age verification measures, enhancing the system for flagging and reporting prohibited content, and developing a more effective system to identify and flag content related to e-cigarettes.

Systematic review and meta-analysis of text messaging interventions to support tobacco cessation.

OBJECTIVE: To review randomised controlled trials (RCTs) investigating the effectiveness of text message-based interventions for smoking cessation, including the effects of dose (number of text messages) and concomitant use of behavioural or pharmacological interventions. DATA SOURCES: We searched seven databases (PubMed, CINAHL, PsycINFO, Scopus, EMBASE, Cochrane Library and Web of Science), Google Scholar and the reference lists of relevant publications for RCTs. Eligible studies included participants aged ≥15 years who smoked tobacco at enrolment. STUDY SELECTION: One reviewer screened titles and abstracts and two reviewers independently screened full texts of articles. DATA EXTRACTION: One of three reviewers independently extracted data on study and intervention characteristics and smoking abstinence rates using Qualtrics software. DATA SYNTHESIS: 30 of the 40 included studies reported higher rates of smoking cessation among those receiving text messaging interventions compared with comparators, but only 10 were statistically significant. A meta-analysis of seven RCTs found that participants receiving text messages were significantly more likely to quit smoking compared with participants in no/minimal intervention or 'usual care' conditions (risk ratio 1.87, 95% CI 1.52 to 2.29, p <0.001). Three trials found no benefit from a higher dose of text messages on smoking cessation. Two trials that tested the added benefit of text messaging to pharmacotherapy reported outcomes in favour of adding text messaging. CONCLUSIONS: Findings suggest that text messaging-based interventions are effective at promoting smoking cessation. Further research is required to establish if any additional benefit is gained from an increased number of text messages or concurrent pharmacotherapy or behavioural counselling.

A systematic review of second-hand smoking mass media campaigns (2002-2022).

BACKGROUND: Second-hand smoking (SHS) increases the risk of chronic disease in adults and poses a serious health threat to children. Mass media campaigns are instrumental in raising awareness and reducing SHS exposure. There is a need to identify recent SHS mass media campaigns and assess their sustainability in terms of knowledge, attitudes, and behavioural changes. This systematic review summarises the characteristics and outcomes of mass media campaigns on SHS prevention. METHODS: PubMed, Embase, Web of Science, and grey literature were searched in November 2022 for SHS campaigns implemented between 2016 and 2022. The eligibility criteria included campaigns on the dangers or effects of SHS with any target group, dissemination medium, study design, or language. The database search identified 1,413 peer-reviewed titles, of which 82 full-texts were screened, with 14 meeting the eligibility criteria. The grey literature search identified 9,807 sources, of which 61 were included. We extracted data on the campaign characteristics, metrics, and smoking-related outcomes. The JBI critical appraisal tool was used to assess the risk of bias of the included studies. RESULTS: We found 73 SHS campaigns conducted between 2002 and 2022, across 50 countries. The campaigns reached 378 million people. The reported recall rates range from 8 to 76%. Of the 11 studies that reported smoking-related outcomes, 10 reported increased knowledge in understanding SHS risks (73-85%), five reported an increased prevalence of smoke-free homes, and two reported an increase in number of participants persuading others to quit smoking. Two studies reported a decrease in overall smoking, whereas three studies observed a reduction in smoking in the presence of children. CONCLUSION: The available data provide some support for the effectiveness of SHS campaigns in reducing smoking behaviours in homes and around children. However, the certainty of evidence was low due to the lack of a control group and the substantial heterogeneity in the outcomes assessed. Future campaigns need comprehensive evaluation and reporting to reduce publication bias.

Transitions to polysubstance use: Prospective cohort study of adolescents in Australia.

BACKGROUND AND AIMS: Adolescent polysubstance use has been associated with adverse social and health outcomes. Our aim was to measure rates and transitions to polysubstance use during adolescence and identify factors associated with initiation and discontinuation of polysubstance use. DESIGN: Prospective cohort study. Multistate Markov modelling was used to estimate rates and identify correlates of transitions between substance use states. SETTING AND PARTICIPANTS: Adolescent-parent dyads (n = 1927; adolescents in grade 7, age ≈13 years) were recruited from Australian schools during 2010/11 (Wave 1). Adolescents were surveyed annually until 2016/17 (n = 1503; age ≈19 years; Wave 7) and parents were surveyed annually until 2014/15 (Wave 5). MEASUREMENTS: Alcohol, tobacco, cannabis and 3,4-methylenedioxymethamphetamine (MDMA) use outcomes were collected at Waves 3-7. Potential confounders were collected at Waves 1-6 and consisted of sex, anxiety and depression symptoms and externalizing problems, parental monitoring, family conflict and cohesion, parental substance use and peer substance use. Covariates were age and family socioeconomic status. FINDINGS: Few adolescents engaged in polysubstance use at earlier waves (Wave 3: 5%; Wave 4: 8%), but proportions increased sharply across adolescence (Waves 5-7: 17%, 24%, 36%). Rates of transitioning to polysubstance use increased with age, with few (<9%) adolescents transitioning out. More externalizing problems (odds ratio [OR] = 1.10; 99.6% confidence interval [CI] = 1.07-1.14), parental heavy episodic drinking (OR = 1.22; 99.6% CI = 1.07-1.40), parental illicit substance use (OR = 3.56; 99.6% CI = 1.43-8.86), peer alcohol use (OR = 5.68; 99.6% CI = 1.59-20.50) and peer smoking (OR = 4.18; 99.6% CI = 1.95-8.81) were associated with transitioning to polysubstance use. CONCLUSIONS: Polysubstance use in Australia appears to be rare during early adolescence but more common in later adolescence with low rates of transitioning out. Externalizing problems and greater parental and peer substance use are risk factors for adolescent polysubstance use that may be suitable intervention targets.

Human cytomegalovirus modulates mTORC1 to redirect mRNA translation within quiescently infected monocytes.

Human cytomegalovirus (HCMV) utilizes peripheral blood monocytes as a means to systemically disseminate throughout the host. Following viral entry, HCMV stimulates non-canonical Akt signaling leading to the activation of mTORC1 and the subsequent translation of select antiapoptotic proteins within infected monocytes. However, the full extent to which the HCMV-initiated Akt/mTORC1 signaling axis reshapes the monocyte translatome is unclear. We found HCMV entry alone was able to stimulate widescale changes to mRNA translation levels and that inhibition of mTOR, a component of mTORC1, dramatically attenuated HCMV-induced protein synthesis. Although monocytes treated with normal myeloid growth factors also exhibited increased levels of translation, mTOR inhibition had no effect, suggesting HCMV activation of mTOR stimulates the acquisition of a unique translatome within infected monocytes. Indeed, polyribosomal profiling of HCMV-infected monocytes identified distinct prosurvival transcripts that were preferentially loaded with ribosomes when compared to growth factor-treated cells. Sirtuin 1 (SIRT1), a deacetylase that exerts prosurvival effects through regulation of the PI3K/Akt pathway, was found to be highly enriched following HCMV infection in an mTOR-dependent manner. Importantly, SIRT1 inhibition led to the death of HCMV-infected monocytes while having minimal effect on uninfected cells. SIRT1 also supported a positive feedback loop to sustain Akt/mTORC1 signaling following viral entry. Taken together, HCMV profoundly reshapes mRNA translation in an mTOR-dependent manner to enhance the synthesis of select factors necessary for the survival of infected monocytes.IMPORTANCEHuman cytomegalovirus (HCMV) infection is a significant cause of morbidity and mortality among the immunonaïve and immunocompromised. Peripheral blood monocytes are a major cell type responsible for disseminating the virus from the initial site of infection. In order for monocytes to mediate viral spread within the host, HCMV must subvert the naturally short lifespan of these cells. In this study, we performed polysomal profiling analysis, which demonstrated HCMV to globally redirect mRNA translation toward the synthesis of cellular prosurvival factors within infected monocytes. Specifically, HCMV entry into monocytes induced the translation of cellular SIRT1 to generate an antiapoptotic state. Defining the precise mechanisms through which HCMV stimulates survival will provide insight into novel anti-HCMV drugs able to target infected monocytes.

Participation in Australian drug treatment programs for individuals engaging in high-risk substance use: Data from a nationally representative sample.

INTRODUCTION: Substance use, including drugs, alcohol and smoking have a significant health, social and economic impact. We aim to assess the rate and factors associated with treatment access among individuals with high-risk substance use. METHOD: This study is a cross-sectional analysis of the 2019 Australian National Drug Strategy Household Survey (N = 22,015). Participants were persons with high-risk substance use based on the Alcohol, Smoking and Substance Involvement Screening Test-Lite (ASSIST-Lite) and current smokers. We measured self-reports of past 12-month engagement in a tobacco, alcohol or other drugs treatment program. RESULTS: Overall, 0.4% had high-risk drug use (0.3% cannabis, 0.1% meth/amphetamine or 0.1% opioids), 7.4% had high-risk alcohol use, and 14.0% currently smoked. Among high-risk users, past 12-month treatment access rates were 50.6% [22.3-78.9%] for opioids, 27.1% [8.1-46.1%] for meth/amphetamine, 14.5% [4.3-24.7%] for cannabis, 9.6% [8.1-11.0%] for alcohol and 11.7% [10.6-12.9%] for current smoking. The primary source of treatment support was information and education (12.7% drugs, 4.6% alcohol, 4.0% smoking), followed by counselling (6.7% drugs, 4.5% alcohol, 3.0% smoking). Online or internet support was accessed by 5.9% (drug) and 1.6% (alcohol) people with high-risk use. Psychological distress was associated with treatment access (drugs: odds ratio 3.03 [0.77-11.95], p = 0.111; alcohol: odds ratio 3.16 [2.20-4.56], p ≤ 0.001; smoking: odds ratio 1.95 [1.52-2.49], p ≤ 0.001). DISCUSSION AND CONCLUSIONS: The proportion of people engaging in risky substance use who had used treatment programs remains low, especially for alcohol. Public health strategies to scale up treatment access are warranted.

Prevalence and correlates of positive parental attitudes towards cannabis use and use intention in Australia during 2016 and 2019.

INTRODUCTION: With recent policy changes around medicinal cannabis in Australia, there is concern about the influence of changing norms of cannabis use on adults who are actively parenting. METHODS: This repeated cross-sectional population study used National and Drug Strategy and Household Surveys to estimate the changes and correlates of cannabis-related attitudes (support of legalisation, approve of regular use, would try or use if legal) among Australian parents from 2016 to 2019. RESULTS: The estimated proportion of parents who supported legalisation and approved regular cannabis use increased significantly. Parents who would try cannabis if it was legal grew from 5.9% (95 %CI: 5.2, 6.7) to 8.1% (95 %CI: 7.2, 9.0). Parents who said they would use cannabis more often increased from 1.6 (95 % CI: 1.2, 1.9) to 2.9 (95 %CI: 2.4, 3.4), an 81% jump in the three years. The strongest associations were observed between a very high level of psychological distress and regular smoking and drinking. For example, people with a very high level of psychological distress were 2.16 times (95 %CI: 1.42, 3.28) and 2.48 times (95 %CI: 1.61, 3.83) more likely to approve legalisation and regular cannabis use, respectively. Daily drinking was associated with higher odds of trying cannabis (OR = 1.66; CI: 1.25-2.20). DISCUSSION AND CONCLUSION: The proportion of parents who would try or use cannabis more often represents a sizeable pool of potential new and frequent users. This highlights the need for education and intervention strategies for parents who use cannabis and care for young children. The associations between mental health and substance use suggest that more research is needed to understand the impact of legalisation on vulnerable groups.

Analysis of wastewater from 2013 to 2021 detected a recent increase in nicotine use in Queensland, Australia.

Previous wastewater-based epidemiology (WBE) studies have reported decreasing trends of nicotine and tobacco use in Australia before 2017, but there is concern that increasing illicit use of nicotine in vaping products and illicit tobacco could reverse this progress. This study aimed to assess temporal trends of nicotine consumption and specifically tobacco consumption via wastewater analysis in a population in Australia between 2013 and 2021. One week of daily wastewater samples were analyzed every two months from February 2013 to December 2021 in a regional city serving ∼100,000 people. A total of 340 daily samples were analyzed for anabasine (tobacco specific biomarker) and nicotine metabolites, cotinine and hydroxycotinine, using direct injection method by liquid chromatography with tandem mass spectrometry. Daily consumption estimates were calculated from daily flow data, population estimates and previously reported excretion factors. Linear spline regression was performed to identify periods when significant change of slopes occurred and to evaluate the temporal trends. Tobacco use monitored using anabasine as a biomarker, showed a decreasing trend over the whole period with a higher rate of decrease during the first two years (2013-2014, 21 % decrease) compared to the later 7 years (2015-2021, 10 % decrease). Nicotine use, monitored using cotinine and hydroxycotinine, showed a downward trend between 2013 and 2018 (2013-2014: 18 % decrease, p < 0.05; 2015-2016: 6 % increase, p = 0.48; Feb-Dec 2017: 15 % decrease, p = 0.39) followed by a significant increase from 2018 to 2021 (40 % increase, p < 0.001). This finding suggests the increasing use of non-tobacco nicotine-based products. Additionally, the tobacco use estimate by wastewater analysis was higher than the tobacco sales data, which suggests the use of illicit tobacco in the catchment.

Conversational artificial intelligence interventions to support smoking cessation: A systematic review and meta-analysis.

Background: Conversational artificial intelligence (chatbots and dialogue systems) is an emerging tool for tobacco cessation that has the potential to emulate personalised human support and increase engagement. We aimed to determine the effect of conversational artificial intelligence interventions with or without standard tobacco cessation interventions on tobacco cessation outcomes among adults who smoke, compared to no intervention, placebo intervention or an active comparator. Methods: A comprehensive search of six databases was completed in June 2022. Eligible studies included randomised controlled trials published since 2005. The primary outcome was sustained tobacco abstinence, self-reported and/or biochemically validated, for at least 6 months. Secondary outcomes included point-prevalence abstinence and sustained abstinence of less than 6 months. Two authors independently extracted data on cessation outcomes and completed the risk of bias assessment. Random effects meta-analysis was conducted. Results: From 819 studies, five randomised controlled trials met inclusion criteria (combined sample size n = 58,796). All studies differed in setting, methodology, intervention, participants and end-points. Interventions included chatbots embedded in multi- and single-component smartphone apps (n = 3), a social media-based (n = 1) chatbot, and an internet-based avatar (n = 1). Random effects meta-analysis of three studies found participants in the conversational artificial intelligence enhanced intervention were significantly more likely to quit smoking at 6-month follow-up compared to control group participants (RR = 1.29, 95% CI (1.13, 1.46), p < 0.001). Loss to follow up was generally high. Risk of bias was high overall. Conclusion: We found limited but promising evidence on the effectiveness of conversational artificial intelligence interventions for tobacco cessation. Although all studies found benefits from conversational artificial intelligence interventions, results should be interpreted with caution due to high heterogeneity. Given the rapid evolution and potential of artificial intelligence interventions, further well-designed randomised controlled trials following standardised reporting guidelines are warranted in this emerging area.

Tumor-wide RNA splicing aberrations generate immunogenic public neoantigens.

T-cell-mediated immunotherapies are limited by the extent to which cancer-specific antigens are homogenously expressed throughout a tumor. We reasoned that recurrent splicing aberrations in cancer represent a potential source of tumor-wide and public neoantigens, and to test this possibility, we developed a novel pipeline for identifying neojunctions expressed uniformly within a tumor across diverse cancer types. Our analyses revealed multiple neojunctions that recur across patients and either exhibited intratumor heterogeneity or, in some cases, were tumor-wide. We identified CD8+ T-cell clones specific for neoantigens derived from tumor-wide and conserved neojunctions in GNAS and RPL22 , respectively. TCR-engineered CD8 + T-cells targeting these mutations conferred neoantigen-specific tumor cell eradication. Furthermore, we revealed that cancer-specific dysregulation in splicing factor expression leads to recurrent neojunction expression. Together, these data reveal that a subset of neojunctions are both intratumorally conserved and public, providing the molecular basis for novel T-cell-based immunotherapies that address intratumoral heterogeneity.

Adolescent Exposure to Online Advertisements and Promotions for Tobacco Products on the Internet-A Cross-Sectional Analysis of the Global Youth Tobacco Surveys.

PURPOSE: Although many countries have banned tobacco advertising on traditional media platforms, the tobacco industry actively promotes their products via online channels. Adolescents are at high risk of exposure due to spending substantial time online. We examined the prevalence of adolescent exposure to online tobacco advertisements and promotions. METHODS: We analyzed data from the Global Youth Tobacco Surveys (GYTS; 2013-2018; average response rate = 76.8%). We included 15 countries in four regions that measured self-reported exposure to tobacco advertising on the internet in the past month (N = 111,356, adolescents aged 11-18): Region of the Americas (Argentina, Costa Rica, Cuba, Ecuador, Panama, Paraguay, Peru), African (Mauritius, Zimbabwe), European (Czech Republic, Turkey), and the Western Pacific (Micronesia, Macao, Papua New Guinea, Samoa). We calculated the prevalence of online exposure to tobacco advertising by past-month cigarette use. RESULTS: Prevalence of adolescent exposure to online advertisements for tobacco products ranged from 18.2%-34.3% and 12.3%-34.4% for tobacco advertisements that "looked fun or cool". Exposure to online tobacco product advertisements was prevalent across countries, including those with advertising bans in place, and included adolescents who have never smoked (14.4%-28.4% exposed to any, 9.1%-31.0% exposed to fun or cool advertisements). Reporting seeing tobacco advertising online that looked fun or cool was positively associated with the prevalence of past-month smoking (r = 0.64, p = .010). DISCUSSION: A substantial proportion of adolescents in countries that have banned tobacco advertising are still exposed to advertisements for tobacco products online. Internet tobacco advertising needs better enforcement to prevent adolescent tobacco use and uptake worldwide.

Use of flavored cannabis vaping products in the US, Canada, Australia, and New Zealand: findings from the international cannabis policy study wave 4 (2021).

Background: Vaping is an increasingly popular mode of cannabis use. Few studies have characterized the role of flavors in cannabis e-liquids.Objectives: To explore the prevalence of flavored vaping liquids, including differences between countries and correlates of use.Methods: Data were from Wave 4 (2021) of the International Cannabis Policy Study with national samples aged 16-65 in Canada, the United States (US), Australia, and New Zealand. The sample comprised 52,938 respondents, including 6,265 who vaped cannabis e-liquids in the past 12-months (2,858 females, 3,407 males). Logistic regression models examined differences in the use of flavored e-liquids between countries and sociodemographic characteristics.Results: The prevalence of vaping cannabis e-liquids was highest in the US (15.3%) and Canada (10.7%) compared to Australia (4.0%) and New Zealand (3.7%). Among past 12-month cannabis consumers, 57.5% reported using flavored vaping liquids, 34.2% used unflavored vaping products and 8.3% did not know. People who vape in Australia were most likely to report using flavored liquids compared to New Zealand (OR = 2.29), Canada (OR = 3.14), and the US (OR = 3.14) (p < .05 for all). Fruit was the most reported vaping flavor (40.8%), followed by candy/dessert (20.4%) and vanilla (15.2%). Use of flavored vapes was greater among younger, ethnic minorities, female, higher education and income adequacy, and more frequent consumers (p < .05).Conclusion: Many cannabis consumers reported using flavored e-liquids, with highest levels among young people aged 16-35. Given the high prevalence of vaping in legal markets, regulators should consider the role of flavored vaping products in promoting cannabis use among this group.

Self-reported depression and anxiety and healthcare professional interactions regarding smoking cessation and nicotine vaping: Findings from 2018 International Tobacco Control Four Country Smoking and Vaping (ITC 4CV) Survey.

INTRODUCTION: People with mental health conditions are disproportionately affected by smoking-related diseases and death. The aim of this study was to assess whether health professional (HP) interactions regarding smoking cessation and nicotine vaping products (NVPs) differ by mental health condition. METHODS: The cross-sectional 2018 International Tobacco Control Four Country (Australia, Canada, England, United States) Smoking and Vaping Survey data included 11040 adults currently smoking or recently quit. Adjusted weighted logistic regressions examined associations between mental health (self-reported current depression and/or anxiety) and visiting a HP in last 18 months; receiving advice to quit smoking; discussing NVPs with a HP; and receiving a recommendation to use NVPs. RESULTS: Overall, 16.1% self-reported depression and anxiety, 7.6% depression only, and 6.6% anxiety only. Compared with respondents with no depression/anxiety, those with depression (84.7%, AOR=2.65; 95% CI: 2.17-3.27), anxiety (82.2%, AOR=2.08; 95% CI: 1.70-2.57), and depression and anxiety (87.6%, AOR=3.74; 95% CI: 3.19-4.40) were more likely to have visited a HP. Among those who had visited a HP, 47.9% received advice to quit smoking, which was more likely among respondents with depression (AOR=1.58; 95% CI: 1.34-1.86), and NVP discussions were more likely among those with depression and anxiety (AOR=1.63; 95% CI: 1.29-2.06). Of the 6.1% who discussed NVPs, 33.5% received a recommendation to use them, with no difference by mental health. CONCLUSIONS: People with anxiety and/or depression who smoke were more likely to visit a HP than those without, but only those with depression were more likely to receive cessation advice, and only those with depression and anxiety were more likely to discuss NVPs. There are missed opportunities for HPs to deliver cessation advice. NVP discussions and receiving a positive recommendation to use them were rare overall.

Viral Vaping: A systematic review and meta analysis of e-cigarette and Tobacco-Related social media content and its influence on youth behaviours and attitudes.

AIMS: E-cigarette and tobacco-related content on social media continues to rise from lax restrictions on both personal and promotional posts. This content has been linked to various mechanisms of increased e-cigarette and tobacco use (i.e., lower risk perceptions and increased susceptibility). This study aimed to synthesis the association between exposure to e-cigarette and tobacco-related content and youth behaviours and attitudes. METHODS: A comprehensive search was conducted on PubMed, Scopus, PsycINFO and Web of Science. Studies published post-2004 reporting effect estimates for exposure or engagement with e-cigarette or tobacco content on social media and behaviour or attitude outcomes were included. RESULTS: Thirty-two studies (N = 274,283, aged 9 to 25 years) were included for synthesis. Meta-analyses revealed significant associations between engagement with tobacco content and use (OR 2.21; 95% CI = 1.27-3.82, p =.005; I2 = 96.4%), exposure to tobacco content and never users' lower risk perceptions (OR 0.68; 95% CI = 0.49-0.91; p =.011; I2 = 78.2%), and exposure to e-cigarette content and use (OR 1.37; 95% CI = 0.99-1.88; p = 0.058; I2 = 64.4%). There was no observed relationship between exposure to tobacco content and ever users' risk perceptions (OR 0.83; 95% CI = 0.61-1.13; p =.231; I2 = 83.5%). Qualitative synthesis found significant associations between tobacco exposure and increased current use and pro-tobacco attitudes; e-cigarette exposure and increased susceptibility and lower risk perceptions; tobacco engagement and increased susceptibility; e-cigarette engagement and increased use; dual exposure and increased susceptibility; and dual engagement and increased dual use. Mixed findings were identified for the influence of e-cigarette exposure on attitudes, tobacco exposure on susceptibility, dual exposure on dual use behaviours, and dual engagement on dual susceptibility. CONCLUSIONS: Findings suggest an association between exposure and engagement to e-cigarette or tobacco products on social media and use or pro-use attitudes among youth. Further substantive research in the area of youth-specific use and attitudes following exposure and engagement with e-cigarette and tobacco content is needed to quantify this association.

Inhibition of SIRT2 promotes death of human cytomegalovirus-infected peripheral blood monocytes via apoptosis and necroptosis.

Peripheral blood monocytes are the cells predominantly responsible for systemic dissemination of human cytomegalovirus (HCMV) and a significant cause of morbidity and mortality in immunocompromised patients. HCMV establishes a silent/quiescent infection in monocytes, which is defined by the lack of viral replication and lytic gene expression. The absence of replication shields the virus within infected monocytes from the current available antiviral drugs that are designed to suppress active replication. Our previous work has shown that HCMV stimulates a noncanonical phosphorylation of Akt and the subsequent upregulation of a distinct subset of prosurvival proteins in normally short-lived monocytes. In this study, we found that SIRT2 activity is required for the unique activation profile of Akt induced within HCMV-infected monocytes. Importantly, both therapeutic and prophylactic treatment with a novel SIRT2 inhibitor, FLS-379, promoted death of infected monocytes via both the apoptotic and necroptotic cell death pathways. Mechanistically, SIRT2 inhibition reduced expression of Mcl-1, an Akt-dependent antiapoptotic Bcl-2 family member, and enhanced activation of MLKL, the executioner kinase of necroptosis. We have previously reported HCMV to block necroptosis by stimulating cellular autophagy. Here, we additionally demonstrate that inhibition of SIRT2 suppressed Akt-dependent HCMV-induced autophagy leading to necroptosis of infected monocytes. Overall, our data show that SIRT2 inhibition can simultaneously promote death of quiescently infected monocytes by two distinct death pathways, apoptosis and necroptosis, which may be vital for limiting viral dissemination to peripheral organs in immunosuppressed patients.

Tobacco purchasing in Australia during regular tax increases: findings from the International Tobacco Control Policy Evaluation Project.

OBJECTIVE: We examined Australian tobacco purchasing trends, the average self-reported price paid within each purchase type and the association between type of tobacco product purchased and participant characteristics, including quit intentions, between 2007 and 2020. METHODS: We analysed data collected from adults who smoked factory-made and/or roll-your-own (RYO) cigarettes in nine waves (2007-2020) of the International Tobacco Control Policy Evaluation Project Australia Survey (nsample=5452, nobservations=11 534). The main outcome measures were type of tobacco products purchased: RYO, carton, pack or pouch size and brand segment. Logistic regression, fit using generalised estimating equations, was estimated the association between the outcome and participant characteristics. RESULTS: The reported price-minimising purchasing patterns increased from 2007 to 2020: any RYO (23.8-43.9%), large-sized pack (2007: 24.0% to 2016: 34.3%); shifting from large-sized to small-sized packs (2020: 37.7%), and economy brand (2007: 37.2% to 2020: 59.3%); shifting from large (2007: 55.8%) to small economy packs (2014: 15.3% to 2020: 48.1%). Individuals with a lower income, a higher nicotine dependence level and no quit intention were more likely to purchase RYO and large-sized packs. CONCLUSION: RYO, large-sized packs and products with a low upfront cost (eg, small RYO pouches and small-sized economy brand packs) may appeal to people on low incomes. Australia's diverse tobacco pack and pouch sizes allow the tobacco industry to influence tobacco purchases. Standardising pack and pouch sizes may reduce some price-related marketing and especially benefit people who have a low income, are highly addicted and have no quit intention.

Longitudinal association between exposure to e-cigarette advertising and youth e-cigarette use in the United States.

BACKGROUND AND AIM: E-cigarette marketing strategies are targeting and appealing to youth, particularly through social media. This study examined the longitudinal relationship between recalled exposure to e-cigarette advertisements on social media and across five traditional advertising mediums, and e-cigarette use, a year later. DESIGN: Weighted regression analyses of waves 4 (W4; 2017), 4.5 (W4.5; 2018) and 5 (W5; 2019) from the Population Assessment of Tobacco and Health Study. SETTING: United States. PARTICIPANTS: Youth aged 12-17 years at W4 or W4.5 (N = 16,671). MEASUREMENTS: We examined the association between past 30-day recalled exposure to six different e-cigarette advertisement mediums (gas stations/convenience stores, social media/websites, newspaper/magazines, radio, billboard, TV) in W4.5 and past 30-day and past 12-month e-cigarette use in W5, while controlling for W4 e-cigarette use and covariates such as sociodemographic variables, academic performance, peer cigarette/e-cigarette use and other substance use. Associations between recalled exposure (W4.5) and lifetime use (W5) among e-cigarette naïve youth at W4.5 (N = 8,914) were also assessed. FINDINGS: Past 12-month and past 30-day e-cigarette use was significantly associated with recalled exposure to e-cigarette advertisement on social media/websites (aOR = 1.65 [99.17 %CI = 1.36,1.99; aOR = 1.49 [99.17 %CI = 1.13, 1.97]) and gas stations/convenience stores (aOR = 1.33; [99.17 %CI = 1.11,1.58]; aOR = 1.27 [99.17 %CI = 1.03,1.58]). Exposure to e-cigarette advertisement on social media/websites (aOR = 1.35 [99.17 %CI = 1.04,1.74]) and gas stations/convenience stores (aOR = 1.67 [99.17 %CI = 1.31,2.13]) was significantly associated with lifetime e-cigarette use among baseline youth who were e-cigarette naïve. CONCLUSIONS: Exposure to e-cigarette advertisement on social media/websites and gas stations/convenience stores was associated with youth e-cigarette use a year later. Stricter restrictions on marketing in these mediums is needed to limit youth exposure to e-cigarette marketing messages if we are to reduce e-cigarette use.