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

BACKGROUND: The health consequences of polytobacco use are not well understood. 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) e-cigarettes, and 4) other combustible products (OC; pipes, hookah, and cigars); dual use of 5) e-cigarettes + cigarettes or e-cigarettes + OC, and 6) cigarettes + OC; and 7) polyuse of all three products. The outcome was parent-reported diagnosis of bronchitis, pneumonia, or chronic cough among youth. 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 (Risk Ratio (RR) = 1.83, 95% CI 1.25-2.68), exclusive e-cigarette use (RR = 1.53, 95% CI 1.08-2.15), combustible product + e-cigarette dual use (RR = 1.90, 95% CI 1.18-3.04), cigarettes + OC dual use (RR = 1.96, 95% CI 1.11-3.48), and polytobacco use (RR = 3.06 95% CI 1.67-5.63) were associated with a higher risk of bronchitis, pneumonia, or chronic cough. In additional analyses, we found that the risk ratio for polytobacco use was higher compared to exclusive e-cigarette use (RR 2.01 CI 95% 1.02-3.95), but not higher compared to exclusive cigarette use (RR 1.67 CI 95% 0.85-3.28). CONCLUSION: We found that exclusive, dual, and poly tobacco use were all associated with higher risk of bronchitis, pneumonia, or chronic cough compared to non-current use.

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 lung injuries outbreak, flavour bans, Tobacco 21 and the COVID-19 pandemic. METHODS: Using the Population Assessment of Tobacco and Health Study, we applied a multistate transition model to 28 061 adults in waves 4-5 (2017-2019) and 24 584 adults in waves 5-6 (2019-2021), 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 2017-2019 to 2019-2021, but ENDS initiation did not significantly change. The persistence of ENDS-only use remained high (75%-80% after 1 year). Cigarette-only use transitions remained similar (88% remaining, 7% to non-current use and 5% to dual or ENDS-only use). In contrast, dual use to ENDS-only transitions increased from 9.5% (95% CI 7.3% to 11.7%) to 20.0% (95% CI 17.4% to 22.6%) per year, decreasing the persistence of dual use. The dual to cigarette-only use 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: The persistence of ENDS use among adults remained high in 2019-2021, but a larger fraction of dual users transitioned to ENDS-only use compared with 2017-2019. Because the fraction of cigarette-only users switching to dual use remained low, especially among older adults, the public health implications of this change are minimal.

The Public Health Impact of a Ban on Flavored Cigars: A Decision-Theoretic Policy Framework.

INTRODUCTION: Half of adult cigar users report flavored cigars as their usual brand. The FDA proposed prohibiting "all characterizing flavors in cigars" and "menthol… in cigarettes." We provide evidence on cigar and cigarette transitions and a framework to assess the impact of a U.S. flavored cigar ban. METHODS: Using PATH Waves 1-4, we estimated use patterns and annual transitions among flavored cigars, non-flavored cigars, cigarettes, and among adults aged 18-34 and aged 35+. We also consider ENDS-related transitions. We developed a decision-theoretic framework for examining the impact of a flavored cigar ban alone, and the impact of a flavored cigar with a menthol cigarette ban with and without a non-tobacco flavored ENDS ban. RESULTS: Cigar users exhibited less stable use than cigarette users, with a large portion of cigar users switching to cigarette use each year. Past studies provide limited information on transitions between cigar and ENDS use. Our policy framework suggests that imposing a flavored cigar ban alone may be partially undermined by the substitution of menthol cigarettes for flavored cigars. While adding a menthol cigarette to a flavored cigar ban is expected to improve public health, a simultaneously implemented ENDS may offset some of the gains. DISCUSSION: Our analysis suggests the information necessary to gauge the public health impact of a cigar flavor ban alone and with flavor bans on cigarettes and ENDS. Further research is needed on ENDS vis-a'-vis cigar use, and the impact of enforcement and non-flavor-related policies on flavor ban effectiveness. IMPLICATIONS: Unlike menthol cigarette use and menthol bans, flavored cigar use and flavored cigar bans have received minimal attention. Transitions from cigars, especially dual and flavored use, are generally common compared to cigarettes. Our policy framework suggests important public health impacts. A flavored cigar ban absent a menthol cigarette ban may be partially undermined by the substitution of menthol cigarettes for flavored cigars. Adding a menthol cigarette ban is expected to offset such substitution and improve public health. However, simultaneously adding an ENDS with a flavored cigar and menthol cigarette ban may reduce the public health impact of a menthol cigarette and cigar flavor ban since flavored cigar users would be less able to substitute a lower-risk alternative.

Interaction Between State-Level Cigarette Prices and County-Level Tobacco 21 Coverage on Cigarette Smoking Outcomes Among US Adolescents.

PURPOSE: To examine whether Tobacco 21 (T21) law coverage moderated associations between cigarette prices and adolescent smoking and associated disparities. METHODS: We used nationally representative, repeated cross-sectional 2014-2020 Monitoring the Future study data (n = 20,547-96,083) to examine associations between state-level average cigarette price per pack and county-level T21 coverage (100% vs. < 100%) on past 30-day smoking participation, first and daily cigarette smoking initiation, and smoking intentions in US adolescents in eighth, 10th, and 12th grade. We implemented weighted, grade-stratified, modified Poisson regression models to test for interactions between price and T21 coverage for each outcome. We also tested for disparities by sex, race and ethnicity, parental education, and college educational expectations. RESULTS: Higher cigarette prices were associated with a lower probability of past 30-day smoking participation among eighth graders in counties with < 100% T21 coverage (average marginal effect = -0.003, 95% confidence interval = -0.006, 0.000) but not among eighth graders in counties with 100% T21 coverage (average marginal effect = 0.001, 95% confidence interval = -0.001, 0.004) (p for interaction = 0.005). There were no associations with other smoking outcomes or grades or evidence of differential associations by sociodemographic factors. DISCUSSION: Our findings suggested that higher cigarette prices were associated with lower adolescent smoking among eighth graders living in counties with < 100% T21 coverage. However, no such association was observed in other grades or smoking outcomes. Further investigation is necessary to determine the best combination of policies to reduce adolescent smoking, related sociodemographic disparities, and the use of other tobacco products in areas with fewer tobacco control policies.

Leveraging Data Locality in Quantum Convolutional Classifiers.

Quantum computing (QC) has opened the door to advancements in machine learning (ML) tasks that are currently implemented in the classical domain. Convolutional neural networks (CNNs) are classical ML architectures that exploit data locality and possess a simpler structure than a fully connected multi-layer perceptrons (MLPs) without compromising the accuracy of classification. However, the concept of preserving data locality is usually overlooked in the existing quantum counterparts of CNNs, particularly for extracting multifeatures in multidimensional data. In this paper, we present an multidimensional quantum convolutional classifier (MQCC) that performs multidimensional and multifeature quantum convolution with average and Euclidean pooling, thus adapting the CNN structure to a variational quantum algorithm (VQA). The experimental work was conducted using multidimensional data to validate the correctness and demonstrate the scalability of the proposed method utilizing both noisy and noise-free quantum simulations. We evaluated the MQCC model with reference to reported work on state-of-the-art quantum simulators from IBM Quantum and Xanadu using a variety of standard ML datasets. The experimental results show the favorable characteristics of our proposed techniques compared with existing work with respect to a number of quantitative metrics, such as the number of training parameters, cross-entropy loss, classification accuracy, circuit depth, and quantum gate count.

Birth-cohort patterns of e-cigarette and other tobacco use among adolescents in the US.

BACKGROUND: E-cigarette use has increased considerably among US adolescents. While many studies have described cross-sectional prevalence trends of youth e-cigarette use, less is known about cohort or generational initiation and use patterns. METHODS: We used data from the US National Youth Tobacco Survey (NYTS) from 2014 to 2022 and age-period-cohort models to analyze age-specific patterns of e-cigarette use initiation and prevalence by cohort and calendar. For comparison, we also examined initiation and prevalence for cigarettes, cigars, and smokeless tobacco, using NYTS data from 1999 to 2022. RESULTS: Age-specific e-cigarette initiation and prevalence varied considerably by calendar year and birth cohort. There was a rapid increase in e-cigarette initiation and prevalence starting with the 1995 birth cohort, peaking with the 2005 birth cohort, and showing signs of decline with more recent cohorts. In contrast, there were substantial continuous reductions in cigarette, cigar, and smokeless use initiation and prevalence by birth cohort. While the reductions in cigarette smoking started with the 1980s birth cohorts, cigar and smokeless initiation and prevalence did not decrease until the 1990-1995 cohorts. CONCLUSIONS: Despite their recent emergence, e-cigarette use has varied considerably across US adolescent cohorts. After early increases, e-cigarette use and initiation peaked with the 2005 birth cohort. These patterns are in contrast with the continuous decreases by cohort in cigarette, cigar, and smokeless use and initiation. As the tobacco product landscape continues to evolve, it will be essential to monitor patterns of use of adolescent and young adult cohorts as they age into adulthood.

The Potential Impact of Oral Nicotine Pouches on Public Health: A Scoping Review.

INTRODUCTION: Oral nicotine pouches (ONPs) are a new class of nicotine products. This scoping review summarizes evidence on ONPs and explores their potential public health impact. AIMS AND METHODS: We conducted a structured literature search for empirical studies across three electronic databases through January 10, 2024. Outcomes included ONP product characteristics, use patterns, beliefs and perceptions, toxicity, and marketing and sales. RESULTS: Sixty-two studies were included, 17 were industry-funded. Most studies were from the United States. While large variations across studies were observed in ONP youth prevalence estimates, nationally representative U.S. studies find current use at 1.5% and lifetime use below 2.5% through 2023. Between 35% and 42% of U.S. adolescents and young adults have heard of ONPs, and 9-21% of tobacco-naïve youth were susceptible to trying them. U.S. adult-use estimates varied widely (0.8%-3% current; 3%-16% lifetime use) and were limited to populations with a history of tobacco use. The chemical composition of ONPs suggests fewer harmful/potentially harmful compounds at lower levels than cigarettes and smokeless tobacco (SLT), except formaldehyde. Industry-funded studies find substantially less cytotoxicity compared to cigarettes and suggest that higher nicotine-strength ONPs can deliver nicotine at levels comparable to or higher than SLT or cigarettes, although with slower nicotine release than cigarettes. Evidence on the cytotoxicity of ONPs relative to SLT is mixed. CONCLUSIONS: ONPs appear to be less toxic than cigarettes and deliver comparable nicotine, presenting an alternative for combustible product users, although key data are mainly available from industry-funded studies. Data from independent research is critically needed. Industry marketing of ONPs may encourage initiation in youth and situational and dual use in adults. IMPLICATIONS: The review provides an initial assessment of the potential role of ONPs in harm reduction and aims to determine unintended consequences of their use (youth uptake and dual-use) and identify populations that disproportionately use the product. This information is essential for tobacco regulatory bodies in determining the net public health impact of nicotine pouches.

Evaluating trends in cigarette and HTP use in Japan and measurement issues in the National Health and Nutrition Survey.

INTRODUTION: Studies have reported that the rapid rise in heated tobacco product (HTP) sales in Japan accompanied an accelerated decline in cigarette sales. However, these studies do not distinguish whether those who previously smoked cigarettes became dual users with HTPs (smoking fewer cigarettes) or instead switched completely to HTPs. If HTPs present lower health risks than cigarettes, replacing cigarettes with HTPs is more likely to improve public health than cigarette users continuing as dual users. METHODS: To evaluate the role of HTP introduction relative to smoking prevalence, we examine trends in cigarette prevalence as related to trends in HTP use using Japan's National Health and Nutrition Survey (NHNS) from 2011 to 2019. We develop measures of relative changes in smoking prevalence use by age and gender in the pre-HTP and post-HTP periods. We then analyse prevalence data by year using joinpoint regression to statistically distinguish changes in trend. RESULTS: Compared with the pre-HTP 2011-2014 period, cigarette prevalence decreased more rapidly during the post-HTP 2014-2017 period, particularly among younger age groups. However, the changing format of NHNS questions limits our ability to determine the impact on smoking prevalence, particularly after 2017. CONCLUSIONS: While suggesting that HTPs helped some people who smoke to quit smoking, this study also shows the difficulties in eliciting accurate survey responses about product use and distinguishing the impact of a potentially harm-reducing product in an environment subject to rapidly evolving patterns of use.

Thrombolysis before venoarterial ECMO for high-risk pulmonary embolism: a retrospective cohort study.

PURPOSE: Despite systemic thrombolysis, a few patients with high-risk pulmonary embolism (PE) remain hemodynamically unstable. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is a considerable lifesaving therapy but systemic thrombolysis before cannulation could carry a high risk of hemorrhage and alter the prognosis. METHODS: Between June 2012 and June 2023, we retrospectively analyzed from three intensive care units in Sorbonne University, ECMO-related complications and 90-day mortality for high-risk PE patients who received ECMO without previous systemic thrombolysis compared to those cannulated after systemic thrombolysis failure. Hospital discharge survivors were assessed for long-term health-related quality of life and echocardiographic evaluations. RESULTS: 72 high-risk PE patients [median age 48 (37-61) years, Simplified Acute Physiology Score II (SAPS II) 74 (60-85)] were placed on VA-ECMO for 5 (5-7) days. 31 (43%) patients underwent pre-ECMO thrombolysis (thrombolysis ECMO group, T +) compared to 41 patients (57%, no thrombolysis ECMO group, T-). There was more pre-ECMO cardiac arrest in the thrombolysis ECMO group (94% vs. 67%, p = 0.02). Ninety-day survival was not different between groups (39% vs 46%, log-rank test, p = 0.31). There was no difference in severe hemorrhages (61% vs 59%, p = 1). Twenty-five over 28 patients attended follow-up at a median time of 69 (52-95) months. Long-term quality of life was acceptable and none of them experienced chronic thromboembolic pulmonary hypertension. CONCLUSIONS: Ninety-day survival and bleeding events rates did not differ in patients treated with VA-ECMO after systemic thrombolysis compared to those who were not. Recent systemic thrombolysis, as a single parameter, should not be considered as a contraindication for VA-ECMO in high-risk PE.

The prevalence and mortality risks of PRISm and COPD in the United States from NHANES 2007-2012.

BACKGROUND: We estimated the prevalence and mortality risks of preserved ratio impaired spirometry (PRISm) and chronic obstructive pulmonary disease (COPD) in the US adult population. METHODS: We linked three waves of pre-bronchodilator spirometry data from the US National Health and Nutritional Examination Survey (2007-2012) with the National Death Index. The analytic sample included adults ages 20 to 79 without missing data on age, sex, height, BMI, race/ethnicity, and smoking status. We defined COPD (GOLD 1, 2, and 3-4) and PRISm using FEV1/FVC cut points by the Global Initiative for Chronic Obstructive Lung Disease (GOLD). We compared the prevalence of GOLD stages and PRISm by covariates across the three waves. We estimated adjusted all-cause and cause-specific mortality risks by COPD stage and PRISm using all three waves combined. RESULTS: Prevalence of COPD and PRISm from 2007-2012 ranged from 13.1%-14.3% and 9.6%-10.2%, respectively. We found significant differences in prevalence by sex, age, smoking status, and race/ethnicity. Males had higher rates of COPD regardless of stage, while females had higher rates of PRISm. COPD prevalence increased with age, but not PRISm, which was highest among middle-aged individuals. Compared to current and never smokers, former smokers showed lower rates of PRISm but higher rates of GOLD 1. COPD prevalence was highest among non-Hispanic White individuals, and PRISm was notably higher among non-Hispanic Black individuals (range 31.4%-37.4%). We found associations between PRISm and all-cause mortality (hazard ratio [HR]: 2.3 95% CI: 1.9-2.9) and various cause-specific deaths (HR ranges: 2.0-5.3). We also found associations between GOLD 2 (HR: 2.1, 95% CI: 1.7-2.6) or higher (HR: 4.2, 95% CI: 2.7-6.5) and all-cause mortality. Cause-specific mortality risk varied within COPD stages but typically increased with higher GOLD stage. CONCLUSIONS: The prevalence of COPD and PRISm remained stable from 2007-2012. Greater attention should be paid to the potential impacts of PRISm due to its higher prevalence in minority groups and its associations with mortality across various causes including cancer.

Isoproterenol improves hemodynamics and right ventricle-pulmonary artery coupling after heart transplantation.

Right ventricular failure (RVF) is a major cause of early mortality after heart transplantation (HT). Isoproterenol (Iso) has chronotropic, inotropic, and vasodilatory properties, which might improve right ventricle function in this setting. We aimed to investigate the hemodynamic effects of isoproterenol on patients with post-HT RVF. We conducted a 1-yr retrospective observational study including patients receiving isoproterenol (Iso) and dobutamine for early RVF after HT. A comprehensive multiparametric hemodynamic evaluation was performed successively three times: no isoproterenol, low doses: 0.025 µg/kg/min, and high doses: 0.05 µg/kg/min (henceforth, respectively, called no Iso, low Iso, and high Iso). From June 2022 to June 2023, 25 patients, median [interquartile range (IQR) 25-75] age 54 [38-61] yr, were included. Before isoproterenol was introduced, all patients received dobutamine, and 15 (60%) were on venoarterial extracorporeal membrane oxygenation (VA-ECMO). Isoproterenol significantly increased heart rate from 84 [77-99] (no Iso) to 91 [88-106] (low Iso) and 102 [90-122] beats/min (high Iso, P < 0.001). Similarly, cardiac index rose from 2.3 [1.4-3.1] to 2.7 [1.8-3.4] and 3 [1.9-3.7] L/min/m2 (P < 0.001) with a concomitant increase in indexed stroke volume (28 [17-34] to 31 [20-34] and 33 [23-35] mL/m2, P < 0.05). Effective pulmonary arterial elastance and pressures were not modified by isoproterenol. Pulmonary vascular resistance (PVR) tended to decrease from 2.9 [1.4-3.6] to 2.3 [1.3-3.5] wood units (WU), P = 0.06. Right ventricular ejection fraction/systolic pulmonary artery pressure (sPAP) evaluating right ventricle-pulmonary artery (RV-PA) coupling increased after isoproterenol from 0.8 to 0.9 and 1%·mmHg-1 (P = 0.001). In conclusion, in post-HT RVF, isoproterenol exhibits chronotropic and inotropic effects, thereby improving RV-PA coupling and resulting in a clinically relevant increase in the cardiac index.NEW & NOTEWORTHY This study offers a detailed and comprehensive hemodynamic investigation at the bedside, illustrating the favorable impact of isoproterenol on right ventricular-pulmonary arterial coupling and global hemodynamics. It elucidates the physiological effects of an underused inotropic strategy in a critical clinical scenario. By enhancing cardiac hemodynamics, isoproterenol has the potential to expedite right ventricular recovery and mitigate primary graft dysfunction, thereby reducing the duration of mechanical support and intensive care unit stay posttransplantation.

The potential impact of removing a ban on electronic nicotine delivery systems using the Mexico smoking and vaping model (SAVM).

Objective: To develop the Mexico Smoking and Vaping Model (Mexico SAVM) to estimate cigarette and electronic nicotine delivery systems (ENDS) prevalence and the public health impact of legalizing ENDS use. Methods: SAVM, a cohort-based discrete-time simulation model, compares two scenarios. The ENDS-Restricted Scenario estimates smoking prevalence and associated mortality outcomes under the current policy of an ENDS ban, using Mexico-specific population projections, death rates, life expectancy, and smoking and e-cigarette prevalence. The ENDS-Unrestricted Scenario projects smoking and vaping prevalence under a hypothetical scenario where ENDS use is allowed. The impact of legalizing ENDS use is estimated as the difference in smoking- and vaping-attributable deaths (SVADs) and life-years lost (LYLs) between the ENDS-Restricted and Unrestricted scenarios. Results: Compared to a national ENDS ban, The Mexico SAVM projects that legalizing ENDS use could decrease smoking prevalence by 40.1% in males and 30.9% in females by 2049 compared to continuing the national ENDS ban. This reduction in prevalence would save 2.9 (2.5 males and 0.4 females) million life-years and avert almost 106 (91.0 males and 15.5 females) thousand deaths between 2025 and 2049. Public health gains decline by 43% to 59,748 SVADs averted when the switching rate is reduced by half and by 24.3% (92,806 SVADs averted) with a 25% ENDS risk level from that of cigarettes but increased by 24.3% (121,375 SVADs averted) with the 5% ENDS risk. Conclusions: Mexico SAVM suggests that greater access to ENDS and a more permissive ENDS regulation, simultaneous with strong cigarette policies, would reduce smoking prevalence and decrease smoking-related mortality. The unanticipated effects of an ENDS ban merit closer scrutiny, with further consideration of how specific ENDS restrictions may maximize public health benefits.

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. AIMS AND METHODS: The study sample was restricted to NVP sales from the states neighboring Massachusetts, Rhode Island, and Washington, 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 < .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.