Lessons learned from U.S. rapid antiretroviral therapy initiation programs.

BACKGROUND: Rapid antiretroviral therapy initiation (R-ART) for treatment of HIV has been recommended since 2017, however it has not been adopted widely across the US. PURPOSE: The study purpose was to understand facilitators and barriers to R-ART implementation in the U.S. RESEARCH DESIGN: This was a qualitative design involving semi-structured interviews. STUDY SAMPLE: The study sample was comprised of the medical leadership of nine US HIV clinics that were early implementers of R-ART. DATA COLLECTION AND ANALYSIS: In-depth, semi-structured interviews were performed. The Consolidated Framework for Implementation Research (CFIR) was used to guide thematic analysis. RESULTS: We identified three main content areas: strong scientific rationale for R-ART, buy-in from multiple key stakeholders, and the condensed timeline of R-ART. The CFIR construct of Evidence Strength and Quality was cited as an important factor in R-ART implementation. Buy-in from key stakeholders and immediate access to medications ensured the success of R-ART implementation. Patient acceptance of the condensed timeline for ART initiation was facilitated when presented in a patient-centered manner, including empathetic communication and addressing other patient needs concurrently. The condensed timeline of R-ART presented logistical challenges and opportunities for the development of intense patient-provider relationships. CONCLUSIONS: Results from the analysis showed that R-ART implementation should address the following: 1) logistical planning to implement HIV treatment with a condensed timeline 2) patients' mixed reactions to a new HIV diagnosis and 3) the high cost of HIV medications.

How the Other Half Sees It: E-cigarette Advertising Exposure and Subsequent E-cigarette Use Among U.S. Young Adult Cigarette Smokers.

INTRODUCTION: E-cigarette advertising may benefit young adult cigarette smokers in transitioning to using e-cigarettes. We assessed whether e-cigarette advertising exposure was associated with subsequent e-cigarette use among young adult cigarette smokers. AIMS AND METHODS: Data were from Waves 4 (2016-2018) and 5 (2018-2019) of the nationally representative Population Assessment of Tobacco and Health (PATH) study adult survey. Respondents were young adult established cigarette smokers at Wave 4 (18-34 years; n = 3391) and a subsample of those who tried to quit smoking cigarettes completely in the past year at Wave 5 (n = 1235). Multivariable logistic regressions were used to examine the associations between e-cigarette advertising exposure (by channel of exposure) and subsequent past-year e-cigarette use in general and e-cigarette use to quit smoking cigarettes, controlling for covariates. RESULTS: At Wave 5, 43.4% of smokers reported past-year use of e-cigarettes; and 14.8% of smokers who tried to completely quit smoking reported past-year use of e-cigarettes to quit. E-cigarette advertising exposure was associated with subsequent past-year e-cigarette use (adjusted odds ratio [AOR] = 1.53, p < .0001, 95% confidence interval [CI] = 1.27, 1.86) and past-year use to quit smoking cigarettes (AOR = 1.65, p < .01, 95% CI = 1.19, 2.29). Advertising exposure through brick-and-mortar stores or websites/social media was similarly associated with both e-cigarette use behaviors. DISCUSSION: Exposure to e-cigarette advertising among U.S. young adult established cigarette smokers may be associated with subsequent e-cigarette use and use to quit smoking. More research is needed to understand the features of e-cigarette advertising (eg, discounts, flavors, smoker-targeted claims) that may shape perception and behavior related to e-cigarette use among young adult smokers. IMPLICATIONS: Little is known about the associations between e-cigarette advertising exposure and e-cigarette use among young adult cigarette smokers who may benefit from switching to e-cigarettes. This study found that e-cigarette advertising exposure was positively associated with (1) subsequent e-cigarette use among U.S. young adult established cigarette smokers and (2) subsequent e-cigarette use to quit smoking cigarettes among those who tried to completely quit in the past year. These observed associations were driven by smokers who did not currently use e-cigarettes at baseline. E-cigarette advertising exposure through brick-and-mortar stores or websites/social media was also positively associated with subsequent e-cigarette use behaviors.

Exploring the hypothetical impact of flavored cigar sales restrictions among black young adult cigar smokers: a semi-structured in-depth interview investigation.

This study assessed the hypothetical impact of flavored cigar sales restrictions on cigar smoking among Black young adult cigar smokers (ages 21-29). Forty in-depth interviews were conducted in 2020. Interviews were independently coded and analyzed using thematic analysis. When asked how they would smoke cigars given a flavor sales restriction, half of participants reported they would smoke in the same way, a third would stop or reduce smoking, and a few were unsure of what they would do. Cigar smoking outcome expectancies, preference for flavors, and perceived addictiveness of cigar products may predict cigar smoking change given flavor sales restrictions.

Noticing people, discounts and non-tobacco flavours in e-cigarette ads may increase e-cigarette product appeal among non-tobacco-using young adults.

INTRODUCTION: Young adults new to tobacco (including e-cigarettes) are at an increased risk of e-cigarette use after e-cigarette exposure. This study examined the association between noticing e-cigarette advertising features and perceived product appeal among non-tobacco-using young adults. METHODS: A sample of non-tobacco-using young adults (ages 18-29 years; n=1993) completed an online survey in 2021. We content analysed visible features from 12 e-cigarette ads that represented commonly used e-cigarette brands. Participants viewed the ads and clicked on the areas of the ads that drew their attention. Participants reported e-cigarette product appeal for each ad, including ad liking, product curiosity and use interest. We used generalised estimating equations to examine within-person associations between noticing specific ad features and reporting each and any type of product appeal, adjusting for noticing other features and participant characteristics. RESULTS: Noticing people, discounts, non-tobacco (menthol and mint/fruit) flavours, positive experience claims or product images was positively associated with having any e-cigarette product appeal. Noticing discounts or mint/fruit flavours was also positively associated with e-cigarette use interest. In contrast, noticing nicotine warnings or smoking cessation claims was negatively associated with ad liking and product curiosity. CONCLUSIONS: Attention to several e-cigarette ad features (eg, people, discounts, non-tobacco flavours) was associated with increased e-cigarette product appeal, whereas attention to nicotine warnings and smoking cessation claims was associated with reduced appeal among non-tobacco-using young adults. Restricting appeal-promoting features while strengthening the effects of nicotine warnings and smoker-targeted claims in e-cigarette ads may potentially reduce e-cigarettes' overall appeal among this priority population.

Exploring the Experiences and Perceptions of Cigar Craving and Addiction among Young Adult Black Cigar Smokers.

Black young adults have the highest prevalence of cigar smoking in the U.S. Little is known about how this population perceives addiction to cigar smoking, which may influence long-term smoking and cessation outcomes. This study used semi-structured in-depth interviews to understand cravings, triggers, and perceived addiction from cigar smoking among a purposive sample of Black young adult cigar smokers (N = 40; 21-29 years). An iterative process was used to develop the codebook, and thematic analysis was used to capture findings based on the products predominantly used: cigarillos, large cigars, or blunts. Results suggest that while participants may share similar types of cravings and triggers (e.g., stress) across the use of these products, predominant blunt smokers reported more unique triggers related to relieving physical discomforts. While most participants reported cigars could be addictive to people in general, only a few perceived that they themselves were addicted. Participants who predominantly smoked cigarillos reported high perceived addiction to cigars, while those who predominantly smoked blunts reported low addiction. Education messages are needed to inform young Black adult cigar smokers about the risks and health symptoms of cigar addiction. These efforts may help increase cigar cessation seeking and reduce cigar addiction-related health consequences and disparities among Black populations.

Physical and Sociocultural Community-Level Influences on Cigar Smoking among Black Young Adults: An In-Depth Interview Investigation.

Black young adults experience disparately high rates of cigar use and its health consequences. Little research has explored community-level influences on cigar smoking in this population, especially concerning product-specific influences and cigar smokers' perceptions. We conducted in-depth interviews with 40 Black young adult (ages 21-29) cigar smokers in the Washington, D.C. area and analyzed themes regarding physical and sociocultural community-level factors perceived to influence cigar use. Themes were further analyzed based on participants' predominant cigar products (cigarillos, large cigars, blunts). Participants reported easy access to affordable cigarillos, widespread cigarillo sales and targeted marketing, norms of cigar and blunt smoking for stress relief, socialization, and cultural participation, and ubiquitous cigar and blunt smoking cues, all of which promoted cigar use in their communities. Future research should further explore how community-level influences contribute to disproportionate cigar use among Black young adults. Our findings suggest that programs and policies addressing physical and sociocultural community-level pro-smoking influences may help mitigate cigar smoking disparities.

Cigar-Smoking-Cessation Interest and Experience among Black Young Adults: A Semi-Structured In-Depth Interview Investigation.

Although Black/African American populations have high cigar-smoking prevalence, little is known about cigar-smoking cessation among this group. This study explored the perceptions and experiences of cigar-smoking cessation and assistance received from healthcare providers among forty Black young-adult cigar smokers (ages 21-29). Semi-structured in-depth phone interviews were transcribed and coded. Qualitative data were analyzed by using thematic analysis. Participants mostly smoked cigarillos, large cigars, and blunts. Overall, many regular cigarillo smokers reported interest in quitting eventually, while large-cigar and blunt smokers shared less interest in quitting because they perceived low harm from smoking these products. The reasons for cigar-smoking cessation were health concerns and financial constraints. Most of the participants who attempted to quit cigars did not use any cessation aids. The reasons for relapse included nicotine withdrawal, stress, and easy access. Additionally, most participants reported their healthcare providers did not ask whether they smoked cigars, and even when they knew, little assistance for cigar-smoking cessation was provided. Informing Black cigar smokers of the harm of cigar smoking and encouraging healthcare providers to screen for and assist with cigar-smoking cessation may alleviate the health burden of cigar smoking in this population.

Parental Anti-Smoking Encouragement as a Longitudinal Predictor of Young Adult Cigarette and E-cigarette Use in a US National Study.

INTRODUCTION: Young adulthood is a critical period for the adoption of risk behaviors like tobacco use. Protective factors in adolescence may promote a tobacco-free transition to young adulthood. We examine associations between the frequency of parental anti-smoking encouragement in adolescence and cigarette and e-cigarette use in young adulthood. AIMS AND METHODS: We analyzed data from Waves 1 (2009-2010, 10th grade, mean age = 16.2 years) and 5 (2013-2014 mean age = 20.3 years) of the US nationally representative NEXT Generation Health Study (n = 1718). At Wave 1, participants reported how often their parents or guardians encourage them to not smoke cigarettes (1 = Rarely or Never, 7 = Frequently). We used separate weighted multiple logistic regression models to model Wave 5 past 30-day cigarette and e-cigarette use as functions of the frequency of parental anti-smoking encouragement at Wave 1, adjusting for sociodemographic and parenting factors, initial substance use, and peer tobacco use. RESULTS: The average frequency of parental encouragement to not smoke cigarettes was fairly high (mean = 5.35). At Wave 5, 24.7% and 14.2% of respondents reported cigarette and e-cigarette use in the past 30 days, respectively. Greater frequency of parental anti-smoking encouragement was associated with lower odds of subsequent cigarette smoking (adjusted odds ratio 0.91, 95% confidence interval 0.83, 0.99) but its association with e-cigarette use was not significant (adjusted odds ratio 0.93, 95% confidence interval 0.84, 1.04). CONCLUSIONS: The longitudinal negative association between anti-smoking encouragement and cigarette use suggests that parental anti-tobacco communication could be a long-term protective factor against young adult tobacco use. Our findings may also suggest the importance of product-specific messages in the evolving tobacco use landscape. IMPLICATIONS: This study builds upon prior investigations of parenting in adolescence as a protective factor against young adult risk behavior. We isolate the frequency of anti-smoking encouragement during adolescence as an actionable factor distinct from other parenting variables. Our findings also suggest that message specificity may be an important factor in parental anti-tobacco communication as youth and young adult tobacco use becomes increasingly dominated by e-cigarettes.

Exploring changes in cigar smoking patterns and motivations to quit cigars among black young adults in the time of COVID-19.

INTRODUCTION: The COVID-19 pandemic has disproportionately impacted the Black/African American communities in the U.S. The objective of this study is to understand the change in cigar smoking patterns and motivations to quit cigars during the COVID-19 pandemic among Black young adult cigar smokers. METHODS: During May-June 2020, in-depth telephone interviews were conducted to investigate cigar (i.e., large cigars, cigarillos, filtered cigars, and blunts) smoking behaviors during the pandemic among self-identified, non-Hispanic Black/African American young adult cigar smokers (n = 40; ages 21-29). Interviews were audio-recorded, transcribed verbatim, and coded separately by three coders. Thematic analysis was used to assess thematic patterns arising from the interviews. RESULTS: Most participants reported smoking cigarillos and blunts in higher frequency and quantity to cope with COVID-19-induced stress, anxiety, loneliness, and boredom due to economic losses and physical isolation. Some also reported contextual changes in cigarillo and blunt smoking, including smoking around the clock, smoking immediately after waking up, and smoking an entire cigarillo or blunt in one setting. Very few participants reported motivations to quit cigars during the pandemic. Perceiving higher risks of progressed COVID-19 outcomes did not prompt participants' increased motivations for quitting cigars. CONCLUSIONS: Black young adults in this study increasingly smoked cigarillos and blunts during the COVID-19 pandemic, mainly attributed to daily life stressors. Participants did not have increased motivations for quitting cigars to reduce COVID-19-related risks. Promoting contextually appropriate healthy coping and cigar smoking cessation may minimize COVID-19-related health consequences of cigar smoking and reduce health disparities among Black young adults.

Lysine Demethylase KDM6A in Differentiation, Development, and Cancer.

Lysine demethylase 6A (KDM6A), also known as UTX, belongs to the KDM6 family of histone H3 lysine 27 (H3K27) demethylases, which also includes UTY and KDM6B (JMJD3). The KDM6A protein contains six tetratricopeptide repeat (TPR) domains and an enzymatic Jumonji C (JmjC) domain that catalyzes the removal of di- and trimethylation on H3K27. KDM6A physically associates with histone H3 lysine 4 monomethyltransferases MLL3 (KMT2C) and MLL4 (KMT2D). Since its identification as an H3K27 demethylase in 2007, studies have reported KDM6A's critical roles in cell differentiation, development, and cancer. KDM6A is important for differentiation of embryonic stem cells and development of various tissues. Mutations of KDM6A cause Kabuki syndrome. KDM6A is frequently mutated in cancers and functions as a tumor suppressor. KDM6A is redundant with UTY and functions largely independently of its demethylase activity. It regulates gene expression, likely through the associated transcription factors and MLL3/4 on enhancers. However, KDM6A enzymatic activity is required in certain cellular contexts. Functional redundancy between H3K27 demethylase activities of KDM6A and KDM6B in vivo has yet to be determined. Further understanding of KDM6A functions and working mechanisms will provide more insights into enhancer regulation and may help generate novel therapeutic approaches to treat KDM6A-related diseases.

H3.3K4M destabilizes enhancer H3K4 methyltransferases MLL3/MLL4 and impairs adipose tissue development.

Histone 3 lysine 4 (H3K4) methyltransferases MLL3 and MLL4 (MLL3/4) are required for enhancer activation during cell differentiation, though the mechanism is incompletely understood. We have attempted to address this issue by generating two mouse lines: one expressing H3.3K4M, a lysine-4-to-methionine (K4M) mutation of histone H3.3 that inhibits H3K4 methylation, and the other carrying conditional double knockout of MLL3/4 enzymatic SET domain. Expression of H3.3K4M in lineage-specific precursor cells depletes H3K4 methylation and impairs adipose tissue and muscle development. Mechanistically, H3.3K4M prevents enhancer activation in adipogenesis by destabilizing MLL3/4 proteins but not other Set1-like H3K4 methyltransferases MLL1, MLL2, SET1A and SET1B. Notably, deletion of the enzymatic SET domain in lineage-specific precursor cells mimics H3.3K4M expression, destabilizes MLL3/4 proteins, and prevents adipose tissue and muscle development. Interestingly, destabilization of MLL3/4 by H3.3K4M in adipocytes does not affect adipose tissue maintenance and thermogenic function. Together, our findings indicate that expression of H3.3K4M, or deletion of the enzymatic SET domain, destabilizes enhancer H3K4 methyltransferases MLL3/4 and impairs adipose tissue and muscle development.

Depletion of Nsd2-mediated histone H3K36 methylation impairs adipose tissue development and function.

The epigenetic mechanisms regulating adipose tissue development and function are poorly understood. In this study, we show that depletion of histone H3K36 methylation by H3.3K36M in preadipocytes inhibits adipogenesis by increasing H3K27me3 to prevent the induction of C/EBPα and other targets of the master adipogenic transcription factor peroxisome proliferator-activated receptor-γ (PPARγ). Depleting H3K36 methyltransferase Nsd2, but not Nsd1 or Setd2, phenocopies the effects of H3.3K36M on adipogenesis and PPARγ target expression. Consistently, expression of H3.3K36M in progenitor cells impairs brown adipose tissue (BAT) and muscle development in mice. In contrast, depletion of histone H3K36 methylation by H3.3K36M in adipocytes in vivo does not affect adipose tissue weight, but leads to profound whitening of BAT and insulin resistance in white adipose tissue (WAT). These mice are resistant to high fat diet-induced WAT expansion and show severe lipodystrophy. Together, these results suggest a critical role of Nsd2-mediated H3K36 methylation in adipose tissue development and function.