COVID-19 associated pulmonary aspergillosis in critically-ill patients: a prospective multicenter study in the era of Delta and Omicron variants.

BACKGROUND: During the first COVID-19 pandemic wave, COVID-19-associated pulmonary aspergillosis (CAPA) has been reported in up to 11-28% of critically ill COVID-19 patients and associated with increased mortality. As new SARS-CoV-2 variants emerged, the characteristics of critically ill COVID-19 patients have evolved, particularly in the era of Omicron. The purpose of this study is to investigate the characteristics of CAPA in the era of new variants. METHODS: This is a prospective multicenter observational cohort study conducted in France in 36 participating intensive care units (ICU), between December 7th, 2021 and April 26th 2023. Diagnosis criteria of CAPA relied on European Confederation of Medical Mycology (ECMM)/International Society for Human & Animal Mycology (ISHAM) consensus criteria. RESULTS: 566 patients were included over the study period. The prevalence of CAPA was 5.1% [95% CI 3.4-7.3], and rose to 9.1% among patients who required invasive mechanical ventilation (IMV). Univariable analysis showed that CAPA patients were more frequently immunosuppressed and required more frequently IMV support, vasopressors and renal replacement therapy during ICU stay than non-CAPA patients. SAPS II score at ICU admission, immunosuppression, and a SARS-CoV-2 Delta variant were independently associated with CAPA in multivariable logistic regression analysis. Although CAPA was not significantly associated with day-28 mortality, patients with CAPA experienced a longer duration of mechanical ventilation and ICU stay. CONCLUSION: This study contributes valuable insights into the prevalence, characteristics, and outcomes of CAPA in the era of Delta and Omicron variants. We report a lower prevalence of CAPA (5.1%) among critically-ill COVID-19 patients than previously reported, mainly affecting intubated-patients. Duration of mechanical ventilation and ICU stay were significantly longer in CAPA patients.

Recurrent ventilator-associated pneumonia in severe Covid-19 ARDS patients requiring ECMO support.

OBJECTIVE: To describe ventilator-associated pneumonia (VAP) recurrence in COVID-19 patients requiring extracorporeal membrane oxygenation (ECMO) support, and to evaluate the impact of antimicrobial treatment duration of the first VAP episode on VAP recurrence. METHODS: Adult patients with COVID-19 severe pneumonia on ECMO admitted between March 2020 and January 2022 were retrospectively included. Primary outcome was incidence of VAP recurrence, and secondary outcome was the impact of duration of antimicrobial treatment on VAP recurrence. RESULTS: Among the 252 included patients, 226 (90%) developed a first VAP. Sixteen had lung abscess and were excluded, leaving 210 patients. VAP recurrence occurred in 172 patients (82%), with a median (IQR) time from first VAP to recurrence of 10 (7-13) days. Pseudomonas aeruginosa and Enterobacteriaceae were respectively responsible for 28% and 52% of first VAP, and 51% and 62% of first recurrence episodes. Among the 210 patients with a first VAP, 158 (75%) received a short course of antibiotics [< 8 days, median (IQR) duration 6 (5-7) days] and 52 (25%) received a prolonged course of antibiotics [≥ 8 days, median (IQR) duration 9 (8-10) days]. Estimated cumulative incidence of VAP recurrence, taking into account death and extubation as competing risks, was not different in patients with short- and prolonged-antimicrobial treatment. CONCLUSIONS: In patients with severe Covid-19-ARDS requiring ECMO support, VAP recurrence occurs frequently, with Enterobacteriaceae and Pseudomonas aeruginosa as predominant causative microorganisms. An antimicrobial treatment of ≥ 8 days for the treatment of first VAP episode did not reduce the risk of VAP recurrence, as compared to shorter duration.

Structural determinants of mitochondrial STAT3 targeting and function.

Signal transducer and activator of transcription (STAT) 3 has been found within mitochondria in addition to its canonical role of shuttling between cytoplasm and nucleus during cytokine signaling. Mitochondrial STAT3 has been implicated in modulation of cellular metabolism, largely through effects on the respiratory electron transport chain. However, the structural requirements underlying mitochondrial targeting and function have remained unclear. Here, we show that mitochondrial STAT3 partitions between mitochondrial compartments defined by differential detergent solubility, suggesting that mitochondrial STAT3 is membrane associated. The majority of STAT3 was found in an SDS soluble fraction copurifying with respiratory chain proteins, including numerous components of the complex I NADH dehydrogenase, while a minor component was found with proteins of the mitochondrial translation machinery. Mitochondrial targeting of STAT3 required the amino-terminal domain, and an internal linker domain motif also directed mitochondrial translocation. However, neither the phosphorylation of serine 727 nor the presence of mitochondrial DNA was required for the mitochondrial localization of STAT3. Two cysteine residues in the STAT3 SH2 domain, which have been previously suggested to be targets for protein palmitoylation, were also not required for mitochondrial translocation, but were required for its function as an enhancer of complex I activity. These structural determinants of STAT3 mitochondrial targeting and function provide potential therapeutic targets for disrupting the activity of mitochondrial STAT3 in diseases such as cancer.

Cross-state Border Nicotine Vaping Products Purchase - Early Evidence from State Emergency Sales Restrictions in 2019.

INTRODUCTION: While retail sales and retailer inspection studies generally indicate high compliance with state sales restrictions on Nicotine Vaping Products (NVPs) within the restricted area, studies using survey data generally indicate that most users could readily continue gaining access to restricted NVPs. Our study bridges a gap in the current literature and investigates the potential role of cross-state border purchases to evade state emergency NVP sales restrictions in 2019. METHODS: The study sample was restricted to NVP sales from the states neighboring Massachusetts (MA), Rhode Island (RI), and Washington (WA), three states that implemented all NVP or flavored NVP sales restrictions in 2019. Among these neighboring states, the 2019 weekly county-level NVP sales by flavors (tobacco, mint/menthol, and other flavors) were compiled using Nielsen Scanner data. A quasi-experimental, comparison group pre-post study design was used to study the impacts of NVP sales restrictions on cross-state border NVP purchases. RESULTS: Weekly NVP sales for border counties significantly increased in response to the MA, RI, and WA bans for tobacco flavored (56%, 45%, 14%, respectively), menthol/mint flavored (51%, 2%, 41%, respectively), and other flavored (79%, 3%, 4%, respectively) products, compared to sales for non-border counties (all p-values <0.01). CONCLUSIONS: Our study identified significant cross-state border NVP purchases in all studied states to circumvent NVP emergency sales restrictions in response to the EVALI outbreak. Policymakers should factor in these purchasing behaviors to evade sales restrictions when evaluating any future potential policies at the state or local levels. IMPLICATIONS: While retail sales data and retailer inspections indicate high compliance with Nicotine Vaping Product (NVP) flavor sales restrictions from major retail outlets, survey data obtain mixed findings on the effects of sales restrictions on vaping behaviors. Our study identified a significant increase in cross-state border NVP purchases to circumvent NVP sales restrictions in 2019, consistent across all three settings of Massachusetts, Rhode Island, and Washington. Policymakers should factor in these cross-state border NVP purchases in response to sales restrictions when evaluating any future potential NVP sales restrictions.

Longitudinal associations between exclusive, dual and polytobacco use and respiratory illness among youth.

Background: The health consequences of polytobacco use are still well not understand. We evaluated prospective associations between exclusive, dual, and polytobacco use and diagnosed bronchitis, pneumonia, or chronic cough among US youth. Methods: Data came from Waves 1-5 of the Population Assessment of Tobacco and Health Study. We categorized time-varying past 30-day tobacco use into seven categories: (1) non-current use; exclusive use of 2) cigarettes, 3) electronic nicotine delivery systems (ENDS), or 4) other combustible products (OC; pipes, hookah, and cigars); dual use of 5) ENDS + cigarettes or ENDS + OC 6) cigarettes + OC; or 7) polyuse of all three products. The outcome was incident diagnosis of bronchitis, pneumonia, or chronic cough. We conducted weighted multilevel Poisson models (person n = 17,517, 43,290 observations) to examine the longitudinal exposure-outcome relationship, adjusting for covariates: sex, age, race and ethnicity, parental education, body mass index, secondhand smoke exposure, and household use of combustible products. Results: Compared to nonuse, exclusive cigarette use (Incidence Rate Ratio (IRR) = 1.83, 95% CI 1.25-2.68), exclusive ENDS use (IRR = 1.53, 95% CI 1.08-2.15), combustible product + ENDS dual use (IRR = 1.90, 95% CI 1.18-3.04), cigarettes + OC dual use (IRR = 1.96, 95% CI 1.11-3.48), and polytobacco use (IRR = 3.06 95% CI 1.67-5.63) were associated with a higher incidence of bronchitis, pneumonia, or chronic cough. Conclusion: We found that exclusive, dual, and poly tobacco use was associated with higher incidence of bronchitis, pneumonia, or chronic cough; Moreover, the incidence rate ratio for polytobacco use was higher than the incidence rate ratio for exclusive use compared to non-current use.

General Surgery Residents Improve Efficiency but Not Hospital Length of Stay in Trauma Care.

Background Good Samaritan University Hospital (GSUH) has been preliminary approved to become a Level I Trauma Center. The American College of Surgeons (ACS) requires Level I Trauma Centers to have senior surgery residents on the trauma service. To fulfill this requirement, GSUH has established an affiliation with Stony Brook University Hospital, a tertiary care hospital with an Accreditation Council for Graduate Medical Education-approved five-year postgraduate training program in General Surgery, to have senior surgery residents from their training program rotate and provide care to trauma patients beginning in July of 2021. Numerous studies over the past few decades have shown conflicting results on patient outcomes with resident involvement. A majority of the studies published only evaluated residents who were native to the respective hospitals. Our study evaluated the impact of surgery residents visiting from an outside hospital on hospital length of stay (LOS) in admitted trauma patients. As increased hospital LOS is strongly associated with increased hospital-acquired complications, increased healthcare costs, and poor patient experience, we used this to evaluate the efficiency of our trauma team with the addition of visiting surgery residents. Methodology A retrospective study was conducted utilizing the hospital's trauma registry. Patients were divided into two groups: the first two years before the addition of surgery residents from July 1st, 2019, to June 30th, 2021, and the second two years after the addition of surgery residents from July 1st, 2021, to June 30th, 2023. The primary outcome measured the hospital LOS between the two groups. Pearson's chi-square test was used to analyze all categorical data, and a t-test was used to compare differences in means. Results From July 1st, 2019, to June 30th, 2023, a total of 7,081 patients were admitted to the trauma service: 3,411 in the group with no surgery residents, and 3,670 patients in the group with residents (p = 0.052). The primary outcome, hospital LOS, was not significantly affected by the addition of surgery residents to the trauma service. Hospital LOS before surgery residents was 4.40 days compared to with residents at 4.41 days (p = 0.944). Mortality was significantly decreased with resident involvement at 1.9% compared to no residents at 2.7% (p = 0.017). Interestingly, the Emergency Department LOS was significantly longer in the group with residents, 268.82 minutes vs. 232.19 minutes (p = 0.004). The average New Injury Severity Score was 9.02 in the group with no residents and 9.04 in the group with surgery residents (p = 0.927). The majority of traumas in both groups were blunt trauma 96.5% with no residents vs. 97.1% with residents (p = 0.192). Conclusions The addition of visiting surgery residents to the trauma team did not significantly increase hospital LOS. Ultimately, having visiting residents on the trauma service may enhance resident education without compromising hospital LOS. Training at different hospitals can allow residents to experience different patient populations and different hospital protocols, making them adaptable and more prepared to work in different hospital settings, whether academic or community. Hospitals without their own residency programs could potentially form affiliations with residency programs to meet the ACS requirements, which can bring more patients to their hospitals.

How do users compare the costs between nicotine vaping products and cigarettes? Findings from the 2016-2020 International Tobacco Control United States surveys.

BACKGROUND AND AIMS: Nicotine vaping products (NVPs) can potentially help adult tobacco users quit smoking. This study evaluated how adult consumers compare the costs between NVPs and cigarettes. METHOD: We used data from the US arm of the 2016-2020 International Tobacco Control Four Country Smoking and Vaping (ITC 4CV) surveys to perform a multinomial logit model with two-way fixed effects to measure how perceived cost comparisons are associated with NVP and cigarette taxes, use patterns, NVP device types and individual sociodemographic factors. RESULTS: Higher cigarette taxes are associated with a greater likelihood of perceiving NVPs and cigarettes as costing the same for the overall population and among people who exclusively smoke, and a lower likelihood of perceiving NVPs as more expensive among people who exclusively vape, compared with lower cigarette taxes. Pre-filled cartridge and tank users are more likely to perceive NVPs as less expensive than cigarettes, compared with people who use other types of NVPs. The associations between taxes and perceived cost comparison were more pronounced among males, younger and low-income populations. CONCLUSIONS: Higher cigarette taxes are associated with perceived financial incentives for nicotine vaping products (NVPs) over cigarettes, whereas NVP taxes are not associated with perceived cost comparison between NVPs and cigarettes.

Association between cigar use, with and without cigarettes, and incident diagnosed COPD: a longitudinal cohort study.

BACKGROUND: While regular cigar smoking is believed to carry similar health risks as regular cigarette smoking, the impact of cigar use, alone or in combination with cigarettes, on obstructive pulmonary disease (COPD) has not been well characterized. The purpose of this study was to examine the prospective association between exclusive and dual cigar and cigarette use and incident self-reported diagnosed COPD. METHODS: This study used data from Waves 1-5 (2013-2019) of the Population Assessment of Tobacco and Health (PATH) Study, a nationally representative survey of U.S. adults. Longitudinal data from adults aged 40 to 79 at Wave 1, without a pre-existing COPD diagnosis who participated at follow-up interview were analyzed. A time-varying current tobacco exposure, lagged by one wave and categorized as: (a) never/non-current use; (b) exclusive cigar use; (c) exclusive cigarette use; and (d) dual cigar/cigarette use. Multivariable models adjusted for demographics (age, sex, race or ethnicity, education), clinical risk factors (asthma, obesity), and smoking-related confounders (second-hand smoke exposure, other combustible tobacco product use, e-cigarette use, time since quitting, cigarette pack-years). The incidence of self-reported diagnosed COPD was estimated using discrete-time survival models, using a general linear modeling (GLM) approach with a binomial distribution and a complementary log-log link function. RESULTS: The analytic sample consisted of 9,556 adults with a mean (SD) age of 56 (10.4), who were predominately female (52.8%) and Non-Hispanic White (70.8%). A total of 906 respondents reported a diagnosis of COPD at follow-up. In the fully adjusted model, exclusive cigar use (adjusted hazard ratio (aHR) = 1.57, 95% CI: 0.77, 3.21) was not associated with increased COPD risk compared to non-use, while exclusive cigarette use (aHR = 1.48, 95% CI: 1.13, 1.93) and dual cigar/cigarette use (aHR = 1.88, 95% CI: 1.24, 2.85) were. CONCLUSIONS: Exclusive cigarette use and dual cigar/cigarette use were associated with diagnosed incident COPD. These results suggest that cigars, when used in combination with cigarettes, may be associated with poorer COPD health outcomes. Dual use may promote a higher likelihood of inhaling cigar smoke, and future research would benefit from examining whether inhalation of cigar smoke increases COPD risk.

Corrigendum: Modeling the future of tobacco control: Using SimSmoke to explore the feasibility of the tobacco endgame in Korea.

[This corrects the article DOI: 10.18332/tid/174127.].

Trends in US Adult Smoking Prevalence, 2011 to 2022.

Importance: President Biden recently prioritized the fight against smoking as key to reducing cancer mortality. Objective: To assess trends in smoking and illuminate the association between smoking and reducing deaths due to cancer. Design, Setting, and Participants: This cross-sectional study used responses to National Health Interview Surveys from January 1, 2011, to December 31, 2022, to characterize trends in current smoking for key sociodemographic groups among US adults. Exposures: Age (18-24, 25-39, 40-64, and ≥65 years), family income (<200%, 200%-399%, and ≥400% of the federal poverty level [FPL]), educational level (less than high school, high school degree or General Educational Development, some college, and college degree or above), and race and ethnicity (Black, Hispanic, White, and other). Main Outcomes and Measures: Weighted current smoking prevalence with 95% CIs by analysis group from 2011 to 2022. Average annual percentage change (AAPC) in smoking prevalence by analysis group is calculated using Joinpoint regression. Results: Data from 353 555 adults surveyed by the National Health Interview Surveys from 2011 to 2022 were included (12.6% Black, 15.0% Hispanic, 65.2% White, and 7.3% other race or ethnicity). Overall, smoking prevalence decreased among adults aged 18 to 24 years from 19.2% (95% CI, 17.5%-20.9%) in 2011 to 4.9% (95% CI, 3.7%-6.0%) in 2022 at an AAPC of -11.3% (95% CI, -13.2% to -9.4%), while it remained roughly constant among adults 65 years or older at 8.7% (95% CI, 7.9%-9.5%) in 2011 and 9.4% (95% CI, 8.7%-10.2%) in 2022 (AAPC, -0.1% [95% CI, -0.8% to 0.7%]). Among adults 65 years or older, smoking prevalence increased from 13.0% (95% CI, 11.2%-14.7%) in 2011 to 15.8% (95% CI, 14.1%-17.6%) for those with income less than 200% FPL (AAPC, 1.1% [95% CI, 0.1%-2.1%]) and remained roughly constant with no significant change for those of higher income. Similar age patterns are seen across educational level and racial and ethnic groups. Conclusions and Relevance: This cross-sectional study found that smoking prevalence decreased from 2011 to 2022 in all age groups except adults 65 years or older, with faster decreases among younger than older adults. These findings suggest that the greatest gains in terms of reducing smoking-attributable morbidity and mortality could be achieved by focusing on individuals with low socioeconomic status, as this population has the highest smoking rates and the worst health prospects.

ENDS, Cigarettes, and Respiratory Illness: Longitudinal Associations Among U.S. Youth.

INTRODUCTION: ENDS use is highly prevalent among U.S. youth, and there is concern about its respiratory health effects. However, evidence from nationally representative longitudinal data is limited. METHODS: Using youth (aged 12-17 years) data from Waves 1-5 (2013-2019) of the Population Assessment of Tobacco and Health Study, multilevel Poisson regression models were estimated to examine the association between ENDS use; cigarettes; and diagnosed bronchitis, pneumonia, or chronic cough. Current product use was lagged by 1 wave and categorized as (1) never/noncurrent use, (2) exclusive cigarette use, (3) exclusive ENDS use, and (4) dual ENDS/cigarette use. Multivariable models adjusted for age, sex, race and ethnicity; parental education; asthma; BMI; cannabis use; secondhand smoke exposure; and household use of combustible products. Data analysis was conducted in 2022-2023. RESULTS: A total of 7.4% of respondents were diagnosed with bronchitis, pneumonia, or chronic cough at follow-up. In the multivariable model, exclusive cigarette use (incident rate ratio=1.85, 95% CI=1.29, 2.65), exclusive ENDS use (incident rate ratio=1.49, 95% CI=1.06, 2.08), and dual use (incident rate ratio=2.70, 95% CI=1.61, 3.50) were associated with a higher risk of diagnosed bronchitis, pneumonia, or chronic cough than never/noncurrent use. CONCLUSIONS: These results suggest that ENDS and cigarettes, used exclusively or jointly, increased the risk of diagnosed bronchitis, pneumonia, or chronic cough among U.S. youth. However, dual use was associated with the highest risk. Targeted policies aimed at continuing to reduce cigarette smoking and ENDS use among youth, especially among those with dual use, are needed.

Cigarette Prices and Disparities in Cessation in the United States.

INTRODUCTION: Achieving cessation in people with established smoking patterns remains a challenge. Increasing cigarette prices has been one of the most effective strategies for lowering smoking rates. It remains unclear how effective it has been in encouraging cessation among adults in recent years and how the effectiveness varies by sociodemographic characteristics. METHODS: Using repeated cross-sectional data collected by the Tobacco Use Supplement of the Current Population Survey, we investigate the relationship between cigarette prices and cessation from 2003 to 2019 in adults 25+. We examine the associations between price and cessation in the population overall and by sex, race/ethnicity, and socioeconomic status. RESULTS: We found mixed support for associations between greater local prices and cessation. Unadjusted models showed that greater local prices were associated with greater odds of cessation, but the associations did not persist after controlling for sociodemographic characteristics. The associations did not significantly differ by respondent characteristics. Sensitivity analysis using alternative specifications and retail state price as the main predictor showed similar results. Sensitivity analysis with controls for e-cigarette use in the 2014-2019 period showed that greater local price was associated with cessation among adults with less than a high school degree. When stratified by year of data collection, results show that greater local prices were associated with cessation after 2009. CONCLUSIONS: Overall, the study adds to the conflicting evidence on the effectiveness of increasing prices on smoking cessation among adults with established smoking patterns. IMPLICATIONS: Higher cigarette prices have been one of the most effective tools for lowering smoking prevalence. It remains unclear how effective they are in encouraging adults with established smoking patterns to quit. Results show that greater local prices were associated with higher odds of cessation, but the association did not persist after sociodemographic adjustment. In a sensitivity analysis, greater local price was associated with cessation among people with less than a high school degree in models controlling for e-cigarette use. We also found evidence that greater local price was associated with cessation after 2009. More comprehensive smoke-free coverage was also associated with greater odds of cessation. The study's results highlight that encouraging cessation among adults with an established smoking pattern remains a challenging policy problem even when cigarette prices rise.

Generalized Quantum Convolution for Multidimensional Data.

The convolution operation plays a vital role in a wide range of critical algorithms across various domains, such as digital image processing, convolutional neural networks, and quantum machine learning. In existing implementations, particularly in quantum neural networks, convolution operations are usually approximated by the application of filters with data strides that are equal to the filter window sizes. One challenge with these implementations is preserving the spatial and temporal localities of the input features, specifically for data with higher dimensions. In addition, the deep circuits required to perform quantum convolution with a unity stride, especially for multidimensional data, increase the risk of violating decoherence constraints. In this work, we propose depth-optimized circuits for performing generalized multidimensional quantum convolution operations with unity stride targeting applications that process data with high dimensions, such as hyperspectral imagery and remote sensing. We experimentally evaluate and demonstrate the applicability of the proposed techniques by using real-world, high-resolution, multidimensional image data on a state-of-the-art quantum simulator from IBM Quantum.

The smoking and vaping model, A user-friendly model for examining the country-specific impact of nicotine VAPING product use: application to Germany.

BACKGROUND: Simulation models play an increasingly important role in tobacco control. Models examining the impact of nicotine vaping products (NVPs) and smoking tend to be highly specialized and inaccessible. We present the Smoking and Vaping Model (SAVM),a user-friendly cohort-based simulation model, adaptable to any country, that projects the public health impact of smokers switching to NVPs. METHODS: SAVM compares two scenarios. The No-NVP scenario projects smoking rates in the absence of NVPs using population projections, deaths rates, life expectancy, and smoking prevalence. The NVP scenario models vaping prevalence and its impact on smoking once NVPs became popular. NVP use impact is estimated as the difference in smoking- and vaping-attributable deaths (SVADs) and life-years lost (LYLs) between the No-NVP and NVP scenarios. We illustrate SAVM's adaptation to the German adult ages 18+ population, the Germany-SAVM by adjusting the model using population, mortality, smoking and NVP use data. RESULTS: Assuming that the excess NVP mortality risk is 5% that of smoking, Germany-SAVM projected 4.7 million LYLs and almost 300,000 SVADs averted associated with NVP use from 2012 to 2060. Increasing the excess NVP mortality risk to 40% with other rates constant resulted in averted 2.8 million LYLs and 200,000 SVADs during the same period. CONCLUSIONS: SAVM enables non-modelers, policymakers, and other stakeholders to analyze the potential population health effects of NVP use and public health interventions.

Modeling the future of tobacco control: Using SimSmoke to explore the feasibility of the tobacco endgame in Korea.

INTRODUCTION: We used a simulation model to assess the feasibility of reaching the tobacco endgame target (reducing the smoking prevalence to below 5% by 2050) and explored potential implementation strategies. METHODS: The impact of strengthened tobacco-control policies on smoking prevalence was analyzed using Korea SimSmoke, a discrete-time Markov process. We considered the effects of various scenarios from 2023 and predictions were conducted until 2050. To confirm the stability of the results, deterministic and probabilistic sensitivity analyses were carried out by increasing and decreasing parameter estimates. RESULTS: The implementation of tobacco-control policies in accordance with the WHO MPOWER (Μonitor tobacco use and prevention policies; Protect people from tobacco smoke; Offer help to quit tobacco smoking; Warn of the dangers of tobacco; Enforce bans on tobacco advertising, promotion, and sponsorship; Raise taxes on tobacco) measures were insufficient to achieve the tobacco endgame objective of 5% by 2050. The overall predicted smoking prevalence in 2050 is 4.7% if all policies are fully implemented in accordance with the FCTC guidelines together with a complete ban on the sale of cigarettes to people born after 2003 and annual 10% increases in price. Sensitivity analyses using the varying policy effect assumptions demonstrated the robustness of the simulation results. CONCLUSIONS: For a substantive reduction in smoking prevalence, it is essential to strongly implement the MPOWER strategy. Beyond this foundational step, the eradication of smoking requires a paradigm shift in the perception of conventional tobacco-control policies, including a tobacco-free generation strategy and radical increases in the price of tobacco products.

Changing patterns of cigarette and ENDS transitions in the USA: a multistate transition analysis of adults in the PATH Study in 2017-2019 vs 2019-2021.

Introduction: The use of cigarettes and electronic nicotine delivery system (ENDS) has likely changed since 2019 with the rise of pods and disposables, the outbreak of lung injuries related to vaping THC, flavor bans, and the COVID pandemic. We analyzed patterns of initiation, cessation, and transitions between cigarettes, ENDS, and dual use before and after 2019. Methods: Using the Population Assessment of Tobacco and Health (PATH) Study, we applied a multistate transition model to 28,061 adults in Waves 4-5 (2017-19) and 24,751 adults in Waves 5-6 (2019-21), estimating transition rates for initiation, cessation, and switching products for each period overall and by age group. Results: Cigarette initiation among adults who never used either product decreased from 2017-19 to 2019-21, but ENDS initiation did not significantly change. Persistence of ENDS-only use remained high, with 75-80% still using ENDS only after 1 year. Cigarette-only use transitions remained similar, with about 88% remaining, 7% transitioning to non-current use, and 5% transitioning to dual or ENDS-only use. In contrast, dual use to ENDS-only transitions increased from 9.5% (95%CI: 7.3-11.7%) to 20.1% (95%CI: 17.5-22.7%) per year from 2017-19 to 2019-21, decreasing the persistence of dual use. The dual use to cigarette-only transition remained at about 25%. These changes were qualitatively similar across adult age groups, though adults ages 18-24 years exhibited the highest probability of switching from cigarette-only use to dual use and from dual use to ENDS-only use. Conclusions: Persistence of ENDS use among adults remained high in 2019-21, but a larger fraction of dual users transitioned to ENDS-only use compared to 2017-19. Because the fraction of cigarette-only users switching to dual use remained low, the public health implications of the increased dual use to ENDS-only transition are minimal.

Potential Implications for Tobacco Industry Transformation of the Acquisition of Swedish Match by Philip Morris International.

Philip Morris International's recent purchase of Swedish Match may prove to be a vital tobacco industry development. We focus on PMIs potential progress in moving from primarily selling cigarettes toward primarily selling noncombustible nicotine delivery products (NCNDPs). We also consider the potential contribution of the acquisition to industry transformation whereby other cigarette firms may potentially move toward primarily selling NCNDPs. We examine the potential impact on noncombustible nicotine delivery product use, including nicotine pouches (a major Swedish Match product), e-cigarettes, heated tobacco products, and, most importantly, on sales of the industry's staple, combustible cigarettes. We focus on the United States as a special case, where PMI is limited from entering the cigarette market. Implications: Philip Morris International's purchase of Swedish Match and policies regarding nicotine pouches (NPs) have been overlooked in the tobacco control literature. The acquisition indicates the importance of the NP market to the largest nonstate-owned tobacco company. The acquisition has the potential through pricing and marketing tactics to either encourage or discourage the use of NPs, e-cigarettes, heated tobacco products, and most importantly cigarettes. Due to its inability to sell cigarettes in the United States, PMI will have incentives to use its alternative nicotine delivery products, including its newly acquired NPs, to reduce the sale of cigarettes by other companies. However, the potential effects in other countries, where PMI does sell cigarettes, are less clear. Monitoring and analyzing tobacco company acquisitions is essential to studying future transitions in using different kinds of tobacco products, especially from cigarettes to lower-risk alternative nicotine delivery products.

Donor T cell STAT3 deficiency enables tissue PD-L1-dependent prevention of graft-versus-host disease while preserving graft-versus-leukemia activity.

STAT3 deficiency (STAT3-/-) in donor T cells prevents graft-versus-host disease (GVHD), but the impact on graft-versus-leukemia (GVL) activity and mechanisms of GVHD prevention remains unclear. Here, using murine models of GVHD, we show that STAT3-/- donor T cells induced only mild reversible acute GVHD while preserving GVL effects against nonsusceptible acute lymphoblastic leukemia (ALL) cells in a donor T cell dose-dependent manner. GVHD prevention depended on programmed death ligand 1/programmed cell death protein 1 (PD-L1/PD-1) signaling. In GVHD target tissues, STAT3 deficiency amplified PD-L1/PD-1 inhibition of glutathione (GSH)/Myc pathways that regulate metabolic reprogramming in activated T cells, with decreased glycolytic and mitochondrial ATP production and increased mitochondrial ROS production and dysfunction, leading to tissue-specific deletion of host-reactive T cells and prevention of GVHD. Mitochondrial STAT3 deficiency alone did not reduce GSH expression or prevent GVHD. In lymphoid tissues, the lack of host-tissue PD-L1 interaction with PD-1 reduced the inhibition of the GSH/Myc pathway despite reduced GSH production caused by STAT3 deficiency and allowed donor T cell functions that mediate GVL activity. Therefore, STAT3 deficiency in donor T cells augments PD-1 signaling-mediated inhibition of GSH/Myc pathways and augments dysfunction of T cells in GVHD target tissues while sparing T cells in lymphoid tissues, leading to prevention of GVHD while preserving GVL effects.