The prospective relationship between a-priori intentions for and patterns of e-cigarette use among adults who smoke cigarettes.

BACKGROUND: Electronic (e-)cigarettes may help adult cigarette smokers achieve cigarette cessation, depending on patterns of e-cigarette use. Among cigarette smokers who do not use e-cigarettes, it is unclear if and how a-priori intentions for use are related to uptake patterns. Longitudinal studies have focused on established e-cigarette users or adolescent and young adult populations exclusively. METHODS: Within a nationwide randomized clinical trial (N = 638), adult cigarette smokers not currently using e-cigarettes were randomized (2:1) to receive (or not) one-month sampling of e-cigarettes. An exploratory factor analysis (EFA) was performed on an established 15-item measure assessing a-priori intentions for e-cigarette use to identify latent variables. Among those receiving e-cigarette products, regression models examined relationships between intentions and: 1) uptake (yes/no), 2) frequency (number of days per week), and 3) amount (puffing episodes per day) of e-cigarette use at one-month follow-up. RESULTS: Two factors emerged from the EFA: 1) cigarette-related intentions (e.g., cigarette cessation, no smell) and 2) novel appeal of e-cigarettes (e.g., flavors). Three items remained and were treated as separate intentions: "feels like cigarette smoking", "curiosity", and "affordability". In the final multivariable models, "feel like cigarette smoking" predicted more frequent e-cigarette use (ß = 0.187, SE = 0.086, p = 0.03); however, none of the five factors/intentions were significantly associated with uptake or amount of use. CONCLUSIONS: For adult cigarette smokers not currently using e-cigarettes, a-priori intentions for using e-cigarettes might not be predictive of if or how these products will be used in the future, suggesting that motives may not drive use behavior.

Adaptation of the Mycobacterium tuberculosis transcriptome to biofilm growth.

Mycobacterium tuberculosis (M. tb), the causative agent of tuberculosis (TB), is a leading global cause of death from infectious disease. Biofilms are increasingly recognized as a relevant growth form during M. tb infection and may impede treatment by enabling bacterial drug and immune tolerance. M. tb has a complicated regulatory network that has been well-characterized for many relevant disease states, including dormancy and hypoxia. However, despite its importance, our knowledge of the genes and pathways involved in biofilm formation is limited. Here we characterize the biofilm transcriptomes of fully virulent clinical isolates and find that the regulatory systems underlying biofilm growth vary widely between strains and are also distinct from regulatory programs associated with other environmental cues. We used experimental evolution to investigate changes to the transcriptome during adaptation to biofilm growth and found that the application of a uniform selection pressure resulted in loss of strain-to-strain variation in gene expression, resulting in a more uniform biofilm transcriptome. The adaptive trajectories of transcriptomes were shaped by the genetic background of the M. tb population leading to convergence on a sub-lineage specific transcriptome. We identified widespread upregulation of non-coding RNA (ncRNA) as a common feature of the biofilm transcriptome and hypothesize that ncRNA function in genome-wide modulation of gene expression, thereby facilitating rapid regulatory responses to new environments. These results reveal a new facet of the M. tb regulatory system and provide valuable insight into how M. tb adapts to new environments.

Shift From Smoking Cigarettes to Vaping Nicotine in Young Adults.

This survey study assesses trends in nicotine use among young adults in the US between 2013 and 2021.

Support for nicotine reduction in cigarettes: findings from the 2016 and 2020 ITC Four Country Smoking and Vaping Surveys.

INTRODUCTION: The USA and New Zealand have sought to establish a product standard to set a maximum nicotine level for cigarettes to reduce their addictiveness. This study examined support for very low nicotine cigarettes (VLNCs) in Australia, Canada, England and the USA between 2016 and 2020. METHODS: Repeated cross-sectional data were analysed from participants who currently smoke, formerly smoked or vaped and/or currently vape in the 2016 (n=11 150) and/or 2020 (n=5432) International Tobacco Control (ITC) Four Country Smoking and Vaping Survey. Respondents were asked if they would support a law that reduces the amount of nicotine in cigarettes to make them less addictive. Adjusted and weighted logistic regression analyses estimated the prevalence and predictors of support, such as country, age, sex, education, income, race and smoking/vaping status for VLNCs (support vs oppose/do not know). RESULTS: A majority of respondents supported a VLNC law, with support highest in Canada (69%; 2016 and 2020 combined), followed by England (61%), Australia (60%) and the USA (58%). Overall, support decreased from 62% in 2016 to 59% in 2020 (p=0.004), which did not differ by country. Levels of support differed by smoking/vaping status, where those who exclusively smoked daily showed the lowest level of support (59%) and those who exclusively vaped non-daily had the highest level of support (72%). CONCLUSION: More than half of respondents in all four countries-including those who smoked daily-supported a hypothetical VLNC standard to render cigarettes less addictive. It is important to examine if support is sustained after policies are implemented.

Symptom Burden of Patients with Chronic Obstructive Pulmonary Disease Attending the Westmead Breathlessness Service: Prevalence, Associations, and Sex-Related Differences.

Purpose: Chronic obstructive pulmonary disease (COPD) is a progressive disease resulting in a range of symptoms including breathlessness. "Symptom burden" describes the severity and impact of multiple symptoms in an individual and is best quantified using validated symptom instruments but is not routinely measured in clinical practice. Therefore, we wanted to assess overall symptom burden in patients with moderate-to-severe COPD and find associated independent predictors. Patients and methods: A single-centre cross-sectional study of patients with COPD who attended the Westmead Breathlessness Service between March 2017 and May 2022 was conducted. We obtained baseline demographic data, lung function, assessed quality of life (CAT), anxiety/depression (HADS), and measured symptom burden (CMSAS). We compared variables between men and women using unpaired t tests or Mann-Whitney tests for continuous variables, and Fisher's exact tests for categorical variables. We used multiple regression to look for independent predictors of overall symptom burden. Data were analysed using Stata/IC 15.1. Results: Eighty-nine patients with COPD, mean age 72.6 years, 55% male, mean FEV1 32% predicted, reported an average of 8.9 symptoms including 6.9 physical and 1.6 psychological symptoms. The most common physical symptoms were shortness of breath (100%) and lack of energy (80%), and the most common psychological symptoms were worrying (65%) and feeling anxious (61%). Median CMSAS total score was higher in women than men (1.34 versus 1.04, respectively; p=0.03) with more women experiencing nervousness (p=0.011) and anxiety (p=0.005). Female sex (p=0.003), HADS-Anxiety (p=0.0001), and HADS-Depression (p=0.0001) were independently associated with total CMSAS score in a multiple linear regression model and explained 63% of total CMSAS variability. Conclusion: Very high physical and psychological symptom burden exists among patients with severe COPD. Anxiety, depression, and female sex were independently associated with increasing symptom burden. Identifying and understanding sex differences for COPD symptoms, and interventions targeting anxiety and depression may help to reduce overall symptom burden within this population.

Barriers to spirometry in Australian general practice: A systematic review.

BACKGROUND AND OBJECTIVES: The reasons for the underutilisation of spirometry are unclear. We undertook a systematic review assessing barriers to correct spirometry in Australian general practice. METHOD: PRISMA guidelines were followed. Six databases (MEDLINE, EMBASE, CINAHL, Scopus, PubMed, Google Scholar) were searched using terms 'primary health care', 'family physicians', 'family practice', 'general practice', 'primary care', 'Australia' and 'spirometry'. RESULTS: The 11 included studies reported multiple barriers to the use of spirometry in Australian general practice. Barriers for clinicians included spirometry having limited clinical utility in general practice (six studies), a reported low confidence with spirometry (six studies) and demonstrated poor spirometry interpretation skills (two studies). Practice-related barriers were time (six studies), cost (four studies), lack of trained staff (four studies), poor availability (four studies) and poor technique/calibration (two studies). Patient reluctance to attend for spirometry (four studies) was also reported as a barrier. DISCUSSION: To reduce barriers to correct spirometry, its perceived low clinical utility and patient reluctance require remediation. Issues of cost, confidence and competence might be addressed by reimbursement settings and ongoing training.

Effect of unguided e-cigarette provision on uptake, use, and smoking cessation among adults who smoke in the USA: a naturalistic, randomised, controlled clinical trial.

Background: As summarised in the most recent Cochrane review, the few clinical trials on e-cigarettes are largely focused on smoking cessation. We aimed to determine the naturalistic uptake, use, and impact of e-cigarettes among adults who may or may not want to stop smoking. Methods: In this naturalistic, randomised, controlled clinical trial, adult smokers, across the motivational spectrum and with minimal history of e-cigarette use, were recruited online from the general community within 11 cities across the USA. Participants were randomly assigned (2:1) to either receive either a free 4-week supply of flavoured, tank-style e-cigarette, or not. E-cigarette group participants received a battery and device with up to 30 pre-filled tanks, offered among five flavours, with minimal instructions on use. The study's primary purpose was to descriptively assess naturalistic uptake and usage of the e-cigarette, and to secondarily assess its impact on smoking behavior. The latter, assessed through six months of follow-up, included: a) self-reported 7-day point prevalence abstinence, b) incidence of quit attempts, and c) smoking reduction. This trial is registered at ClinicalTrials.gov, NCT03453385. Findings: Between 5/2018 and 3/2022, 638 adult smokers were enrolled and randomly assigned (427 in the e-cigarette group and 211 in the no-product control group). Uptake of e-cigarettes was robust: approximately 70% of participants used the product, with average usage exceeding 4 days per week during the initial 30 days. Based on an intent-to-treat approach where missing data is imputed as smoking, almost all behavioral outcomes favored the e-cigarette group relative to no-product control, including point prevalence abstinence at six months (Odds Ratio [OR] = 1.8; 95% Confidence Interval [CI] = 1.0-3.1), cumulative incidence of 24-hr quit attempts (OR = 1.5; 95% CI = 1.0-2.2), and having reduced smoking by at least 50% since baseline (OR = 1.8; 95% CI = 1.2-2.7). Results were similar under an alternative imputation. Interpretation: Complementing cessation-focused trials, results suggest that unguided e-cigarette use also leads to smoking cessation, allaying the notion that causal effects of e-cigarettes on cessation are not reflective of real-world scenario of self-determined use. For smokers who may not be able to quit using existing pharmacologic approaches, e-cigarettes may be considered to achive that purpose. Funding: National Cancer Institute.

Adaptation of the Mycobacterium tuberculosis transcriptome to biofilm growth.

Mycobacterium tuberculosis ( M. tb ), the causative agent of tuberculosis (TB), is a leading global cause of death from infectious disease. Biofilms are increasingly recognized as a relevant growth form during M. tb infection and may impede treatment by enabling bacterial drug and immune tolerance. M. tb has a complicated regulatory network that has been well-characterized for many relevant disease states, including dormancy and hypoxia. However, despite its importance, our knowledge of the genes and pathways involved in biofilm formation is limited. Here we characterize the biofilm transcriptomes of fully virulent clinical isolates and find that the regulatory systems underlying biofilm growth vary widely between strains and are also distinct from regulatory programs associated with other environmental cues. We used experimental evolution to investigate changes to the transcriptome during adaptation to biofilm growth and found that the application of a uniform selection pressure resulted in loss of strain-to-strain variation in gene expression, resulting in a more uniform biofilm transcriptome. The adaptive trajectories of transcriptomes were shaped by the genetic background of the M. tb population leading to convergence on a sub-lineage specific transcriptome. We identified widespread upregulation of non-coding RNA (ncRNA) as a common feature of the biofilm transcriptome and hypothesize that ncRNA function in genome-wide modulation of gene expression, thereby facilitating rapid regulatory responses to new environments. These results reveal a new facet of the M. tb regulatory system and provide valuable insight into how M. tb adapts to new environments. Importance: Understanding mechanisms of resistance and tolerance in Mycobacterium tuberculosis ( M. tb ) can help us develop new treatments that capitalize on M. tb 's vulnerabilities. Here we used transcriptomics to study both the regulation of biofilm formation in clinical isolates as well as how those regulatory systems adapt to new environments. We find that closely related clinical populations have diverse strategies for growth under biofilm conditions, and that genetic background plays a large role in determining the trajectory of evolution. These results have implications for future treatment strategies that may be informed by our knowledge of the evolutionary constraints on strain(s) from an individual infection. This work provides new information about the mechanisms of biofilm formation in M. tb and outlines a framework for population level approaches for studying bacterial adaptation.

"And then I found $5": Optimizing recruitment efficiency in remote clinical trials.

Introduction: As clinical trials adopt remote methodologies, there is need to optimize efficiency of remote enrollment. Within a remote clinical trial, we aim to (1) assess if sociodemographic factors differ among those consenting via mail vs. technology-based procedures (e-consent), (2) determine if, among those consenting via mail, a small unconditional monetary reward ($5) increases likelihood of subsequent enrollment, (3) economically evaluate additional cost per additional participant enrolled with $5 reward. Methods: In the parent nationwide randomized clinical trial of adult smokers (N = 638), participants could enroll via mail or e-consent. Logistic regression models assessed relationships between sociodemographics and enrollment via mail (vs e-consent). Mailed consent packets were randomized (1:4) to include $5 unconditional reward or not, and logistic regression modeling examined impact of reward on subsequent enrollment, allowing for a randomized study within a study. Incremental cost-effectiveness ratio analysis estimated additional cost per additional participant enrolled with $5 incentive. Results: Older age, less education, lower income, and female sex predicted enrolling via mail vs e-consent (p < .05's). In adjusted model, older age (AOR = 1.02, p = .016) and less education (AOR = 2.23, p < .001) remained predictive of mail enrollment. The $5 incentive (vs none) increased enrollment rate by 9% (AOR = 1.64, p = .007), with estimated cost of additional $59 per additional participant enrolled. Conclusions: As e-consent methods become more common, they have potential to reach many individuals but with perhaps diminished inclusion across all sociodemographic groups. Provision of an unconditional monetary incentive is possibly a cost-effective mechanism to increase recruitment efficiency for studies employing mail-based consenting procedures.

Inflammatory Cell Dynamics after Murine Femoral Artery Wire Injury: A Multi-Parameter Flow Cytometry-Based Analysis.

An acute inflammatory response following arterial surgery for atherosclerosis, such as balloon angioplasty, stenting, and surgical bypass, is an important driver of neointimal hyperplasia after arterial injury, which leads to recurrent ischemia. However, a comprehensive understanding of the dynamics of the inflammatory infiltrate in the remodeling artery is difficult to attain due to the shortcomings of conventional methods such as immunofluorescence. We developed a 15-parameter flow cytometry method to quantitate leukocytes and 13 leukocyte subtypes in murine arteries at 4 time points after femoral artery wire injury. Live leukocyte numbers peaked at 7 days, which preceded the peak neointimal hyperplasia lesion at 28 days. Neutrophils were the most abundant early infiltrate, followed by monocytes and macrophages. Eosinophils were elevated after 1 day, while natural killer and dendritic cells gradually infiltrated over the first 7 days; all decreased between 7 and 14 days. Lymphocytes began accumulating at 3 days and peaked at 7 days. Immunofluorescence of arterial sections demonstrated similar temporal trends of CD45+ and F4/80+ cells. This method allows for the simultaneous quantitation of multiple leukocyte subtypes from small tissue samples of injured murine arteries and identifies the CD64+Tim4+ macrophage phenotype as being potentially important in the first 7 days post-injury.

E-Cigarette Screening in Primary Care.

INTRODUCTION: Primary care visits present an opportune time to assess behaviors that contribute to patient health. Smoking, alcohol use, and illicit drugs are routinely documented in electronic health records, but less is known about screening for E-cigarette use and the prevalence of E-cigarette use in primary care settings. METHODS: Data include 134,931 adult patients who visited 1 of 41 primary care clinics within a 12-month period (June 1, 2021-June 1, 2022). Data on demographics, combustible tobacco, alcohol, illicit drug, and E-cigarette use were extracted from electronic medical records. Logistic regression was utilized to examine the variables associated with differential odds of being screened for E-cigarette use. RESULTS: Rates of E-cigarette screening (n=46,997; 34.8%) were significantly lower than that of tobacco (n=134,196; 99.5%), alcohol (n=129,766; 96.2%), and illicit drug (n=129,766; 92.6%) use. Of those assessed for E-cigarette use, 3.6% (n=1,669) reported current use. Of those with documented nicotine use (n=7,032), 17.2% (n=1,207) used mono E-cigarettes exclusively, 76.3% (n=5,364) used combustible tobacco exclusively, and 6.6% (n=461) reported dual use (both E-cigarette use and combustible tobacco use). Those who used combustible tobacco or illicit substances as well as younger patients were more likely to have been screened for E-cigarette use. CONCLUSIONS: Overall rates of E-cigarette screening were significantly lower than those of other substances. The use of combustible tobacco or illicit substances was associated with an increased likelihood of being screened. This finding may be because of the relatively recent proliferation of E-cigarettes, the recent addition of E-cigarette documentation to the electronic health record, or a lack of training on screening for E-cigarette use.

Structural competency in New Mexico: Moving outside of medical education.

ABSTRACTIn 2019, the Doña Ana Wellness Institute (DAWI), Doña Ana County, New Mexico's health council, sponsored two trainings in structural competency by the Structural Competency Working Group. One focused on health care professionals and learners; the other focused on government, non-profit organisations, and elected officials. DAWI and New Mexico Human Services Department (HSD) representatives attended the trainings and identified the structural competency model as useful for the health equity work both groups were already engaging. These trainings provided the foundation for DAWI and HSD to develop additional trainings, programmes, and curricula founded on structural competency and focused on supporting health equity work.This article describes how DAWI and HSD used the structural competency framework to deepen our work, including how we have expanded the concept beyond its original orientation to support strategic planning, improve communication, and build structurally competent communities. We illustrate how the framework strengthened our existing community and state work and how we adapted the model to better fit our work. Adaptations included changes in language, the use of the lived experiences of organisation members as a foundation for structural competency education, and a recognition that policy work happens at multiple levels and in multiple ways for organisations.

E-cigarette cessation and transitions in combusted tobacco smoking status: longitudinal findings from the US FDA PATH Study.

BACKGROUND AND AIMS: Electronic nicotine delivery systems (ENDS) can help people to quit smoking combusted tobacco products (CTPs), but most current and former smokers who use ENDS also intend to quit ENDS. This analysis measured whether ENDS cessation among current and former CTP smokers is associated with changes in CTP smoking or abstinence. DESIGN: Regression analysis of a nationally representative cohort from waves 4 (W4) and 5 (W5) of the Population Assessment of Tobacco and Health Study (December 2016-November 2019). SETTING: United States. PARTICIPANTS: Adults (n = 1525) who reported W4 current or former use of ≥ 1 CTP and either currently using ENDS or quitting ENDS in the past year were included. MEASUREMENTS: Logistic regressions were performed separately among W4 current and former CTP smokers, controlling for demographic and tobacco use characteristics. First, we analyzed proximal outcomes by testing the association between ENDS quit status and CTP abstinence, both occurring during W5. Next, we analyzed long-term outcomes by testing W4 ENDS quit status as a predictor of CTP abstinence at W5, approximately 1 year later. FINDINGS: Among W4 current CTP smokers, there was no evidence that CTP smoking abstinence differed between those quitting or continuing using ENDS, both in our proximal [adjusted odds ratio (aOR) = 1.37, 95% confidence interval (CI) = 0.90, 2.10] and long-term (aOR = 0.90, 95% CI = 0.52, 1.53) analyses. Among former CTP smokers, quitting ENDS was associated with less CTP abstinence in our proximal analysis (aOR = 0.42, 95% CI = 0.20, 0.89), but there was no evidence that CTP smoking abstinence differed between those quitting or continuing using ENDS in our long-term analysis (aOR = 0.86, 95% CI = 0.44, 1.67). CONCLUSIONS: There is no evidence that ENDS cessation is associated with CTP abstinence among current smokers, although mixed findings among former smokers indicate a possible risk for relapse to smoking associated with quitting ENDS.

Is perception reality? Associations among "light" cigarettes and number of cigarettes smoked per day.

INTRODUCTION: Cigarette filter ventilation and light descriptors are associated with lowered perceptions of risk and smoking more cigarettes per day (CPD). This study examined the relationship between usual cigarette ventilation, perception, and CPD. METHODS: A crowdsourced sample (N = 995) of individuals who smoke higher-ventilated (=>20% ventilation) or lower-ventilated (=<10% ventilation) cigarettes identified their usual cigarette as "light" or "full flavor", and reported their average CPD. RESULTS: We found: 1) no association between ventilation status and perception of light versus full flavor (AUC=0.58), with the inaccurate perception being more prevalent in younger individuals (p = 0.041) and those who smoke L&M (73%, p < 0.001) and Camel (61%, p = 0.006) brands; and 2) perception, but not ventilation of usual cigarette, was significantly associated with CPD (p = 0.006), with individuals who perceived their cigarettes as light reporting an average of 13% more cigarettes per day (2.6 CPD), compared to those who perceived their cigarette as full flavor. CONCLUSIONS: Perceptions of light versus full-flavor, but not ventilation status, predicted CPD. These findings may inform anti-smoking health communication strategies and smoking cessation interventions. IMPLICATIONS: Tobacco control policies should eradicate the perception of cigarettes as light or full-flavored. Future research investigating the associations between cigarette filter ventilation and smoking behavior should consider the confounding effects that may lie in an individual's perceptions of their cigarettes.

Uncovering undernutrition in chronic obstructive pulmonary disease: Beyond body mass index.

BACKGROUND: Undernutrition, a common but treatable complication of chronic obstructive pulmonary disease (COPD), contributes to poor outcomes but is under-detected. Improved detection could prompt dietary intervention which may improve outcomes. We investigated whether adding a measure of muscle mass (fat-free mass index, FFMI) or a malnutrition screening tool (Mini Nutritional Assessment, MNA®) to the commonly used measure of body mass index (BMI), helps detect undernutrition in COPD. METHODS: We conducted a retrospective chart review of 86 outpatients with COPD. Demographic and disease severity data were collected, and nutritional status assessed using BMI, FFMI and MNA®. RESULTS: Patients comprised 55% males with median age 71.5 years, severe COPD (median FEV1 = 0.74 (30.5% predicted)) and high symptom impact (median COPD Assessment Test (CAT) = 23). Twenty-eight percent of patients had low BMI, 27% had low FFMI, 22% were MNA®-classified malnourished and 43% were MNA®-classified at risk of malnutrition. MNA® correlated moderately with BMI and classified 55% of patients with healthy/high BMI as either malnourished or at risk of malnutrition. FFMI and BMI correlated strongly, and low FFMI was present in 5% of patients with healthy/high BMI. The undernutrition measures also showed weak to moderate correlations with disease severity (spirometry data) and MNA® weakly correlated with symptom impact (CAT). CONCLUSION: The MNA® identified more undernourished patients than FFMI or BMI. It also correlated with disease severity and broader symptom burden. The MNA® appears to be a simple tool for earlier detection of patients who may benefit from dietary intervention, potentially enhancing their quality of life.

Monoamine oxidase inhibition in cigarette smokers: From preclinical studies to tobacco product regulation.

Monoamine oxidase (MAO) activity is reduced in cigarette smokers and this may promote the reinforcing actions of nicotine, thereby enhancing the addictive properties of cigarettes. At present, it is unclear how cigarette smoking leads to MAO inhibition, but preclinical studies in rodents show that MAO inhibition increases nicotine self-administration, especially at low doses of nicotine. This effect of MAO inhibition develops slowly, likely due to plasticity of brain monoamine systems; studies relying on acute MAO inhibition are unlikely to replicate what happens with smoking. Given that MAO inhibition may reduce the threshold level at which nicotine becomes reinforcing, it is important to consider this in the context of very low nicotine content (VLNC) cigarettes and potential tobacco product regulation. It is also important to consider how this interaction between MAO inhibition and the reinforcing actions of nicotine may be modified in populations that are particularly vulnerable to nicotine dependence. In the context of these issues, we show that the MAO-inhibiting action of cigarette smoke extract (CSE) is similar in VLNC cigarettes and cigarettes with a standard nicotine content. In addition, we present evidence that in a rodent model of schizophrenia the effect of MAO inhibition to enhance nicotine self-administration is absent, and speculate how this may relate to brain serotonin systems. These issues are relevant to the MAO-inhibiting effect of cigarette smoking and its implications to tobacco product regulation.