Incidence and risk factors for colorectal cancer in Africa: a systematic review and meta-analysis.

INTRODUCTION: Colorectal cancer (CRC) is the second leading cause of cancer-related death worldwide. There is a significant burden of mortality from colorectal cancer in Africa. Due to the heterogeneity of dietary and lifestyle practices throughout Africa, our work sought to define risk factors for the development of CRC in the African continent. METHODS: We systematically searched PubMed, Embase, Global Health, CINAHL, Cochrane CENTRAL, and African Index Medicus for studies written in English, examining the incidence and risk factors of CRC in Africa. A systematic analysis was done to compare different risk factors in constituent studies. A meta-analysis random effects model was fitted to estimate the pooled incidence of CRC. RESULTS: Of 2471 studies screened, 26 were included for the quantitative analysis; 20 in the incidence analysis, and six in the risk factor analysis. The overall ASIR per 100,000 person-years of CRC for males and females was 7.51 and 6.22, respectively. The highest incidence rates were observed between 2012 and 2021. Risk factors for CRC in Africa include tobacco smoking, and consumption of red meat, butter, and alcohol. Protective factors included, regular consumption of fruits and regular physical activity. CONCLUSION: The incidence of CRC in Africa is higher than that suggested by previous studies. Our study shows that nonmodifiable and modifiable factors contribute to CRC in Africa. High-quality studies conducted on generalizable populations that examine risk factors in a comprehensive fashion are required to inform primary and secondary prevention initiatives for CRC in Africa.

End TB strategy: Role of tobacco control.

Tobacco use and Tuberculosis (TB) presents a huge public health challenge globally. Tobacco and TB have consistent and strong epidemiological evidence with smokers having higher odds of TB infection, disease, mortality, delayed diagnosis etc. Overall, limited evidence exists about the extent of TB-tobacco integration. The aim of the current short communication is to highlight comprehensive strategy for addressing TB-tobacco comorbidities.

Gene regulatory networks reveal sex difference in lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) has been observed to have significant sex differences in incidence, prognosis, and response to therapy. However, the molecular mechanisms responsible for these disparities have not been investigated extensively. METHODS: Sample-specific gene regulatory network methods were used to analyze RNA sequencing data from non-cancerous human lung samples from The Genotype Tissue Expression Project (GTEx) and lung adenocarcinoma primary tumor samples from The Cancer Genome Atlas (TCGA); results were validated on independent data. RESULTS: We found that genes associated with key biological pathways including cell proliferation, immune response and drug metabolism are differentially regulated between males and females in both healthy lung tissue and tumor, and that these regulatory differences are further perturbed by tobacco smoking. We also discovered significant sex bias in transcription factor targeting patterns of clinically actionable oncogenes and tumor suppressor genes, including AKT2 and KRAS. Using differentially regulated genes between healthy and tumor samples in conjunction with a drug repurposing tool, we identified several small-molecule drugs that might have sex-biased efficacy as cancer therapeutics and further validated this observation using an independent cell line database. CONCLUSIONS: These findings underscore the importance of including sex as a biological variable and considering gene regulatory processes in developing strategies for disease prevention and management.

Lung adenocarcinoma (LUAD) is a disease that affects males and females differently. Biological sex not only influences chances of developing the disease, but also how the disease progresses and how effective various therapies may be. We analyzed sex-specific gene regulatory networks consisting of transcription factors and the genes they regulate in both healthy lung tissue and in LUAD and identified sex-biased differences. We found that genes associated with cell proliferation, immune response, and drug metabolism are differentially targeted by transcription factors between males and females. We also found that several genes that are drug targets in LUAD, are also regulated differently between males and females. Importantly, these differences are also influenced by an individual's smoking history. Extending our analysis using a drug repurposing tool, we found candidate drugs with evidence that they might work better for one sex or the other. These results demonstrate that considering the differences in gene regulation between males and females will be essential if we are to develop precision medicine strategies for preventing and treating LUAD.

The association of tobacco smoking and metabolite levels in the anterior cingulate cortex of first-episode psychosis patients: A case-control and 6-month follow-up 1H-MRS study.

Tobacco smoking is highly prevalent among patients with psychosis and associated with worse clinical outcomes. Neurometabolites, such as glutamate and choline, are both implicated in psychosis and tobacco smoking. However, the specific associations between smoking and neurometabolites have yet to be investigated in patients with psychosis. The current study examines associations of chronic smoking and neurometabolite levels in the anterior cingulate cortex (ACC) in first-episode psychosis (FEP) patients and controls. Proton magnetic resonance spectroscopy (1H MRS) data of 59 FEP patients and 35 controls were analysed. Associations between smoking status (i.e., smoker yes/no) or cigarettes per day and Glx (glutamate + glutamine, as proxy for glutamate) and total choline (tCh) levels were assessed at baseline in both groups separately. For patients, six months follow-up data were acquired for multi-cross-sectional analysis using linear mixed models. No significant differences in ACC Glx levels were found between smoking (n = 28) and non-smoking (n = 31) FEP patients. Smoking patients showed lower tCh levels compared to non-smoking patients at baseline, although not surving multiple comparisons correction, and in multi-cross-sectional analysis (pFDR = 0.08 and pFDR = 0.044, respectively). Negative associations were observed between cigarettes smoked per day, and ACC Glx (pFDR = 0.02) and tCh levels (pFDR = 0.02) in controls. Differences between patients and controls regarding Glx might be explained by pre-existing disease-related glutamate deficits or alterations at nicotine acetylcholine receptor level, resulting in differences in tobacco-related associations with neurometabolites. Additionally, observed alterations in tCh levels, suggesting reduced cellular proliferation processes, might result from exposure to the neurotoxic effects of smoking.

The role of tobacco smoking in anti-neutrophil cytoplasmic antibody-associated vasculitis: a systematic review.

OBJECTIVES: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are a group of systemic pauci-immune necrotising vasculitides involving small vessels, characterised by the presence of specific ANCA autoantibodies directed to leukocyte proteinase 3 (PR3-ANCA) or myeloperoxidase (MPO-ANCA) and subdivided into three clinical entities: granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA). The aetiology of AAV is unknown and many genetic, epigenetic and environmental factors have been reported to be involved in pathogenesis. Smoking is widely recognised as a risk factor for the development of many autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus. This systematic review will analyse known data about the role of smoking in the development, clinical presentation and outcome of AAV. METHODS: Articles that examined interactions between tobacco smoking and AAV (GPA, MPA, EGPA) were included. All articles selected were in English. No limitation on publication date was established. Case reports were excluded. The systematic search was performed using PubMed/Medline and Cochrane Library databases. RESULTS: The search provided a total of 131 articles. Three studies were added, obtained from the review of the reference lists of articles. 70 were removed because they were duplicated or written in languages other than English. The title and abstract of 64 articles were screened. Of these, 30 were excluded as the title and/or abstract did not meet the inclusion criteria. Thus, 34 remained for full-text review, of which 8 were excluded. 26 articles were therefore included in this review. The role of smoking in AAV development is unclear. AAV patients current smoking appear appear to be younger and more frequently males, with a lower prevalence of EGPA and MPA than GPA. Ever smokers show higher relapse rate. Smoking seems to be associated with a higher risk of cardiovascular events during follow-up. Smokers incur an increased risk of infections. Finally, many data support smoking as a risk factor for end stage renal disease and mortality in AAV patients. CONCLUSIONS: Current data support the hypothesis that smoking influences prevalence, clinical phenotype and prognosis of ANCA-associated vasculitis. However, further studies are required to fully determine its role.

Prevalence of tobacco smoking and associated factors among adults in Ethiopia: a systematic review and meta-analysis.

Introduction: The public health concern of tobacco smoking is more prevalent in low- and middle-income countries including Ethiopia. Various studies have investigated tobacco smoking in various parts of Ethiopia. However, the findings have been inconsistent and characterized by significant variability. Besides, there is no nationally representative data on the subject, which could deter the design of effective intervention strategies to reduce tobacco-related problems. Therefore, this study aimed to estimate the pooled prevalence of tobacco smoking and associated factors among adults in Ethiopia. Methods: The study was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols Guideline. A detailed search was conducted from international databases including PubMed, Cochrane Library, Science Direct, CINAHL, African Journals Online, HINARI, Global Health, and Google Scholar. The extracted data was analyzed using STATA 14 software. A random-effects model was used to estimate the effect size. The Egger regression test and I2 statistics were used to determine potential publication bias and heterogeneity among the reviewed articles, respectively. Results: A total of 32 studies with 69,897 study participants were included in this systematic review and meta-analysis. The pooled prevalence of lifetime tobacco smoking among adults in Ethiopia was 16.0% (95% confidence Interval (CI): 13.6-18.39) and there was significant heterogeneity among the included studies (I2 = 99.1%, p < 0.001). Male adults were three times more likely to smoke tobacco as compared with females [OR = 3.22 (95% CI: 2.06-5.03)]. Being an alcohol user [OR = 3.78 (95%CI: 1.27-11.24)] and having tobacco-smoking friends [OR = 7.21 (95%CI: 5.56-9.35)] are potential determinant factors for tobacco smoking. Conclusion: The pooled prevalence of lifetime and current tobacco smoking among adults in Ethiopia was high, which calls for urgent intervention. Therefore, prioritization of tobacco control strategies, such as creating awareness about the public health importance of tobacco smoking, can help prevent and mitigate the effects of tobacco smoking. Alcohol control law enforcement should also be strengthened.

Arrhythmogenic effects of acute electronic cigarette compared to tobacco cigarette smoking in people living with HIV.

The leading cause of death in people living with HIV (PLWH) is cardiovascular disease, and the high prevalence of tobacco cigarette (TC) smoking is a major contributor. Switching to electronic cigarettes (ECs) has been promoted as a harm reduction strategy. We sought to determine if acute EC compared to TC smoking had less harmful effects on arrhythmogenic risk factors including acute changes in hemodynamics, heart rate variability (HRV), and ventricular repolarization (VR). In PLWH who smoke, changes in hemodynamics, HRV, and VR were compared pre/post acutely using an EC, TC, or puffing on an empty straw on different days in random order, in a crossover study. Thirty-seven PLWH (36 males, mean age 40.5 ± 9.1 years) participated. Plasma nicotine was greater after TC versus EC use (10.12 ± 0.96 vs. 6.18 ± 0.99 ng/mL, respectively, p = 0.004). HR increased significantly, and similarly, after acute EC and TC smoking compared to control. Changes in HRV that confer increased cardiac risk (LF/HF ratio) were significantly smaller after acute EC versus TC use, consistent with a harm reduction effect. In a post-hoc analysis of PLWH with and without positive concurrent recreational drug use as indicated by point of care urine toxicology testing, this differential effect was only seen in PLWH not currently using recreational drugs. Changes in VR were not different among the three exposures. In PLWH who smoke, EC compared to TC smoking resulted in smaller adverse changes in HRV. This differential effect was accompanied by a smaller increase in plasma nicotine, and was negated by concurrent recreational drug use. Additional studies are warranted in this vulnerable population disproportionately affected by tobacco-related health disparities.

The effects of aerobic exercise training on inflammatory markers in adult tobacco smokers: A systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: Aerobic exercise training may reduce systemic inflammation, but the effects of this on systemic inflammatory markers in adult tobacco smokers has not been systematically reviewed. Therefore, we evaluated the effects of aerobic exercise training on C-reactive protein (CRP) and tumor necrosis factor-α (TNF-α) in adult tobacco smokers using a systematic review and meta-analysis of randomized controlled trials. METHODS: A comprehensive literature search was carried out using PubMed/Medline, Web of Science, EMBASE, Google Scholar, and hand search of bibliographies of the retrieved English or Persian articles up to August 2023. This review only included randomized controlled trials which investigated the effect of aerobic exercise training on CRP and TNF-α in adult smokers, based on a predefined inclusion and exclusion criteria. RESULTS: A total of 1641 articles were identified. Six studies were included in the review and four evaluated CRP and two evaluated TNF-α in only males. The meta-analysis demonstrated that aerobic exercise training significantly decreased TNF-α concentrations in males (MD = -6.68, 95 % CI = -13.90 to -0.54, P = 0.05). CRP concentrations did not decrease significantly when the data from the four studies were pooled (MD = -0.17, 95 % CI = -0.37 to 0.03, P = 0.09). CONCLUSION: Aerobic exercise training may reduce the concentration of TNF-α in male smokers, but it does not have a significant effect on CRP concentrations. However, these findings are based upon a small number of studies, that enrolled either exclusively male or female participants, and further investigation is necessary to increase statistical inference.

PD-L2 mediates tobacco smoking-induced recruitment of regulatory T cells via the RGMB/NFκB/CCL20 cascade.

Programmed cell death ligand 2 (PD-L2), a ligand for the receptor programmed cell death 1 (PD-1), has an identity of 34% with its twin ligand PD-L1 and exhibits higher binding affinity with PD-1 than PD-L1. However, the role of PD-L2 in non-small cell lung cancer (NSCLC) progression, especially tobacco-induced cancer progression, has not been fully understood. Here, we found that PD-L2 promoted tumor growth in murine models with recruitment of regulatory T cells (Tregs). In patients with NSCLC, PD-L2 expression level in tumor samples was higher than in counterpart normal controls and was positively associated with patients' response to anti-PD-1 treatment. Mechanismly, PD-L2 bound its receptor Repulsive guidance molecule B (RGMB) on cancer cells and activated extracellular signal-regulated kinase (Erk) and nuclear factor κB (NFκB), leading to increased production of chemokine CCL20, which recruited Tregs and contributed to NSCLC progression. Consistently, knockdown of RGMB or NFκB p65 inhibited PD-L2-induced CCL20 production, and silencing of PD-L2 repressed Treg recruitment by NSCLC cells. Furthermore, cigarette smoke and carcinogen benzo(a)pyrene (BaP) upregulated PD-L2 in lung epithelial cells via aryl hydrocarbon receptor (AhR)-mediated transcription activation, whose deficiency markedly suppressed BaP-induced PD-L2 upregulation. These results suggest that PD-L2 mediates tobacco-induced recruitment of Tregs via the RGMB/NFκB/CCL20 cascade, and targeting this pathway might have therapeutic potentials in NSCLC.

[Prevalence of tobacco smoking and related factors in people aged 15 years and above in Beijing, 2014-2021].

Objective: To evaluate the effect of the implementation of Beijing Smoking Control Regulation in 2015 on the smoking prevalence in people aged ≥15 years in Beijing during 2014-2021, and explore factors associated with tobacco use behavior in local population. Methods Using a pooled cross-sectional design, data from Beijing Adult Tobacco Survey in 2014, 2016, 2019 and 2021 (4 surveys) were combined into one dataset. The 4 surveys used same multistage cluster sampling procedure. After complex survey weighting, multiple logistic regression models were constructed to analyze factors influencing smoking status. Results: A total of 8 484, 9 372, 8 534 and 10 551 respondents were included in the surveys in 2014, 2016, 2019 and 2021, respectively. The smoking prevalence rate was 23.4%, 22.3%, 20.3% and 19.9%, respectively, in Beijing residents aged ≥15 years, exhibiting a linear declining trend (P=0.010). Factors associated with current smoking in men were age 25-44 years (OR=2.22, 95%CI: 1.68-2.95) and 45-64 years, (OR=2.64, 95%CI: 2.06-3.39), educational level of high school (OR=0.69, 95%CI: 0.49-0.95) and undergraduate and above (OR=0.46, 95%CI: 0.33-0.63), and awareness of smoking causing stroke (OR=0.71, 95%CI: 0.61-0.81), and awareness of smoking causing lung cancer (OR=0.53, 95%CI: 0.42-0.66), the differences were significant (all P<0.05). After controlling interfering factors, the current smoking prevalence in men in 2019 (OR=0.73, 95%CI: 0.63-0.87, P<0.001) and 2021 (OR=0.72, 95%CI: 0.61-0.88, P<0.001) were significantly lower than that in 2014. Factors associated with current smoking in women were living alone (OR=1.80, 95%CI: 1.33-2.44), educational level of undergraduate and above (OR=0.43, 95%CI: 0.27-0.69), other occupations except doctor and teacher (OR=8.54, 95%CI: 2.80-26.02) or being retired/unemployed (OR=9.39, 95%CI: 3.19-27.65), and awareness of smoking causing cardiovascular events (OR=0.58, 95%CI: 0.39-0.84), and awareness of smoking causing lung cancer (OR=0.54, 95%CI: 0.35-0.83), the differences were significant (all P<0.05). No significant change in smoking status in women was found in 4 surveys. Conclusions: The smoking prevalence rate in men in Beijing has declined since the implementation of Beijing Smoking Control Regulation 5 years, indicating the effectiveness of legislative approach in tobacco control. Socio-demographic factors and the awareness level of tobacco harm could influence smoking status. Future tobacco control programs should target the people with lower education level, young men, women living alone, and those with occupations other than teachers/doctors or the unemployed/retired and include more comprehensive health education.

The Impact of Tobacco Smoking and Alcohol Consumption on the Development of Gastric Cancers.

Chronic infection of Helicobacter pylori is considered the principal cause of gastric cancers, but evidence has accumulated regarding the impact of tobacco smoking and alcohol consumption on the development of gastric cancers. Several possible mechanisms, including the activation of nicotinic acetylcholine receptors, have been proposed for smoking-induced gastric carcinogenesis. On the other hand, local acetaldehyde exposure and ethanol-induced mucosal inflammation have been proposed as the mechanisms involved in the development of gastric cancers in heavy alcohol drinkers. In addition, genetic polymorphisms are also considered to play a pivotal role in smoking-related and alcohol-related gastric carcinogenesis. In this review, we will discuss the molecular mechanisms involved in the development of gastric cancers in relation to tobacco smoking and alcohol consumption.

A Bivariate Twin Study of Lifetime cannabis Initiation and Lifetime Regular Tobacco Smoking Across Three Different Countries.

Regular cigarette smoking and cannabis consumption are strongly positively related to each other, yet few studies explore their underlying variation and covariation. We evaluated the genetic and environmental decomposition of variance and covariance of these two traits in twin data from three countries with different social norms and legislation. Data from the Netherlands Twin Register, FinnTwin12/16, and the Minnesota Center for Twin Family Research (total N = 21,617) were analyzed in bivariate threshold models of lifetime regular smoking initiation (RSI) and lifetime cannabis initiation (CI). We ran unstratified models and models stratified by sex and country. Prevalence of RSI was lowest in the Netherlands and prevalence of CI was highest in Minnesota. In the unstratified model, genetic (A) and common environmental factors (C) contributed substantially to the liabilities of RSI (A = 0.47, C = 0.34) and CI (A = 0.28, C = 0.51). The two liabilities were significantly phenotypically (rP = 0.56), genetically (rA = 0.74), and environmentally correlated in the unstratified model (rC = 0.47and rE = 0.48, representing correlations between common and unique environmental factors). The magnitude of phenotypic correlation between liabilities varied by country but not sex (Minnesota rP ~ 0.70, Netherlands rP ~ 0.59, Finland rP ~ 0.45). Comparisons of decomposed correlations could not be reliably tested in the stratified models. The prevalence and association of RSI and CI vary by sex and country. These two behaviors are correlated because there is genetic and environmental overlap between their underlying latent liabilities. There is heterogeneity in the genetic architecture of these traits across country.

Temporal Trends in Tobacco Smoking Prevalence During the Period 2010-2020 in Vietnam: A Repeated Cross-Sectional Study.

Objectives: This study used repeated cross-sectional data from three national surveys in Vietnam to determine tobacco smoking prevalence from 2010 to 2020 and disparities among demographic and socioeconomic groups. Methods: Tobacco smoking temporal trends were estimated for individuals aged 15 and over and stratified by demographic and socioeconomic status (SES). Prevalence estimates used survey weights and 95% confidence intervals. Logistic regression models adjusted for survey sample characteristics across time were used to examine trends. Results: Tobacco smoking prevalence dropped from 23.8% in 2010 to 22.5% in 2015 and 20.8% in 2020. The adjusted OR for 2015 compared to 2010 was 0.87, and for 2020 compared to 2010 was 0.69. Smoking decreased less for employed individuals than unemployed individuals in 2020 compared to 2010. Smoking was higher in the lower SES group in all 3 years. Higher-SES households have seen a decade-long drop in tobacco use. Conclusion: This prevalence remained constant in lower SES households. This highlights the need for targeted interventions to address the specific challenges faced by lower-SES smokers and emphasizes the importance of further research to inform effective policies.

Type 2 diabetes patients requiring empagliflozin in Southeast of Iran: Frequency and guideline adherence (2022–2023) / Pacientes con diabetes tipo 2 que requieren empagliflozina en el sureste de Irán: frecuencia y cumplimiento de las directrices (2022-2023)

Introduction: Empagliflozin plays a beneficial role in individuals with type 2 diabetes at high risk of cardiovascular complications. This study aimed to assess the prevalence of individuals with type 2 diabetes who required empagliflozin based on clinical guidelines between the years 2022 and 2023. Material and methods: This study was a descriptive-analytical cross-sectional study conducted on a target population of patients with type 2 diabetes. Patient data, including demographic characteristics, smoking status, hypertension, hyperlipidemia, renal insufficiency, retinopathy, and proteinuria, were collected. The indication for prescribing empagliflozin was determined based on the risk of cardiovascular complications. Results: A total of 398 individuals with type 2 diabetes with a mean age of 58.4 years were examined. Overall, 87.4% of the patients had an indication for empagliflozin prescription. The indication for empagliflozin prescription was significantly higher in men, individuals with hyperlipidemia, those over 55 years of age, obese individuals, and smokers. The mean age, body mass index, and triglyceride levels were higher in candidates for empagliflozin prescription. Male candidates for empagliflozin had significantly higher rates of smoking and systolic blood pressure compared to females. Conclusions: The findings of this study demonstrated that a significant percentage of individuals with type 2 diabetes had an indication for empagliflozin prescription based on clinical and laboratory criteria. (AU)

Introducción: La empagliflozina tiene un papel beneficioso en las personas con diabetes tipo 2 con alto riesgo de complicaciones cardiovasculares. Este estudio tuvo como objetivo evaluar la prevalencia de pacientes con este padecimiento que requerían empagliflozina según las guías clínicas entre los años 2022 y 2023. Material y métodos: Se trata de un estudio transversal descriptivo-analítico realizado en una población objetivo de personas con diabetes tipo 2. Se recogieron los datos de los pacientes, incluyendo las características demográficas, el hábito tabáquico, la hipertensión, la hiperlipidemia, la insuficiencia renal, la retinopatía y la proteinuria. La indicación para prescribir empagliflozina se determinó en función del riesgo de complicaciones cardiovasculares. Resultados: Se examinaron un total de 398 individuos con diabetes tipo 2 con una edad media de 58,4 años. En general, 87,4% de estos tenía una indicación para la prescripción de empagliflozina, la cual fue significativamente mayor en los hombres, aquellos con hiperlipidemia, obesidad, los mayores de 55 años y los fumadores. La edad media, el índice de masa corporal y los niveles de triglicéridos fueron mayores en los candidatos a la prescripción de este medicamento. Los candidatos masculinos a este fármaco tenían tasas significativamente más altas de tabaquismo y presión arterial sistólica, en comparación con las mujeres. Conclusiones: Los resultados de este estudio demostraron que un porcentaje significativo de personas con diabetes tipo 2 tenía una indicación para la prescripción de empagliflozina según los criterios clínicos y de laboratorio. (AU)

Urinary Metabolite Diagnostic and Prognostic Liquid Biopsy Biomarkers of Lung Cancer in Nonsmokers and Tobacco Smokers.

PURPOSE: Nonsmokers account for 10% to 13% of all lung cancer cases in the United States. Etiology is attributed to multiple risk factors including exposure to secondhand smoking, asbestos, environmental pollution, and radon, but these exposures are not within the current eligibility criteria for early lung cancer screening by low-dose CT (LDCT). EXPERIMENTAL DESIGN: Urine samples were collected from two independent cohorts comprising 846 participants (exploratory cohort) and 505 participants (validation cohort). The cancer urinary biomarkers, creatine riboside (CR) and N-acetylneuraminic acid (NANA), were analyzed and quantified using liquid chromatography-mass spectrometry to determine if nonsmoker cases can be distinguished from sex and age-matched controls in comparison with tobacco smoker cases and controls, potentially leading to more precise eligibility criteria for LDCT screening. RESULTS: Urinary levels of CR and NANA were significantly higher and comparable in nonsmokers and tobacco smoker cases than population controls in both cohorts. Receiver operating characteristic analysis for combined CR and NANA levels in nonsmokers of the exploratory cohort resulted in better predictive performance with the AUC of 0.94, whereas the validation cohort nonsmokers had an AUC of 0.80. Kaplan-Meier survival curves showed that high levels of CR and NANA were associated with increased cancer-specific death in nonsmokers as well as tobacco smoker cases in both cohorts. CONCLUSIONS: Measuring CR and NANA in urine liquid biopsies could identify nonsmokers at high risk for lung cancer as candidates for LDCT screening and warrant prospective studies of these biomarkers.

Tobacco smoking, smoking cessation and life expectancy among people with HIV on antiretroviral therapy in South Africa: a simulation modelling study.

INTRODUCTION: As access to effective antiretroviral therapy (ART) has improved globally, tobacco-related illnesses, including cardiovascular disease, cancer and chronic respiratory conditions, account for a growing proportion of deaths among people with HIV (PWH). We estimated the impact of tobacco smoking and smoking cessation on life expectancy among PWH in South Africa. METHODS: In a microsimulation model, we simulated 18 cohorts of PWH with virologic suppression, each homogenous by sex, initial age (35y/45y/55y) and smoking status (current/former/never). Input parameters were from data sources published between 2008 and 2022. We used South African data to estimate age-stratified mortality hazard ratios: 1.2-2.3 (females)/1.1-1.9 (males) for people with current versus never smoking status; and 1.0-1.3 (females)/1.0-1.5 (males) for people with former versus never smoking status, depending on age at cessation. We assumed smoking status remains unchanged during the simulation; people who formerly smoked quit at model start. Simulated PWH face a monthly probability of disengagement from care and virologic non-suppression. In sensitivity analysis, we varied smoking-associated and HIV-associated mortality risks. Additionally, we estimated the total life-years gained if a proportion of all virologically suppressed PWH stopped smoking. RESULTS: Forty-five-year-old females/males with HIV with virologic suppression who smoke lose 5.3/3.7 life-years compared to PWH who never smoke. Smoking cessation at age 45y adds 3.4/2.4 life-years. Simulated PWH who continue smoking lose more life-years from smoking than from HIV (females, 5.3 vs. 3.0 life-years; males, 3.7 vs. 2.6 life-years). The impact of smoking and smoking cessation increase as smoking-associated mortality risks increase and HIV-associated mortality risks, including disengagement from care, decrease. Model results are most sensitive to the smoking-associated mortality hazard ratio; varying this parameter results in 1.0-5.1 life-years gained from cessation at age 45y. If 10-25% of virologically suppressed PWH aged 30-59y in South Africa stopped smoking now, 190,000-460,000 life-years would be gained. CONCLUSIONS: Among virologically suppressed PWH in South Africa, tobacco smoking decreases life expectancy more than HIV. Integrating tobacco cessation interventions into HIV care, as endorsed by the World Health Organization, could substantially improve life expectancy.

Cannabis, Tobacco Use, and COVID-19 Outcomes.

Importance: It is unclear whether cannabis use is associated with adverse health outcomes in patients with COVID-19 when accounting for known risk factors, including tobacco use. Objective: To examine whether cannabis and tobacco use are associated with adverse health outcomes from COVID-19 in the context of other known risk factors. Design, Setting, and Participants: This retrospective cohort study used electronic health record data from February 1, 2020, to January 31, 2022. This study included patients who were identified as having COVID-19 during at least 1 medical visit at a large academic medical center in the Midwest US. Exposures: Current cannabis use and tobacco smoking, as documented in the medical encounter. Main Outcomes and Measures: Health outcomes of hospitalization, intensive care unit (ICU) admission, and all-cause mortality following COVID-19 infection. The association between substance use (cannabis and tobacco) and these COVID-19 outcomes was assessed using multivariable modeling. Results: A total of 72 501 patients with COVID-19 were included (mean [SD] age, 48.9 [19.3] years; 43 315 [59.7%] female; 9710 [13.4%] had current smoking; 17 654 [24.4%] had former smoking; and 7060 [9.7%] had current use of cannabis). Current tobacco smoking was significantly associated with increased risk of hospitalization (odds ratio [OR], 1.72; 95% CI, 1.62-1.82; P < .001), ICU admission (OR, 1.22; 95% CI, 1.10-1.34; P < .001), and all-cause mortality (OR, 1.37, 95% CI, 1.20-1.57; P < .001) after adjusting for other factors. Cannabis use was significantly associated with increased risk of hospitalization (OR, 1.80; 95% CI, 1.68-1.93; P < .001) and ICU admission (OR, 1.27; 95% CI, 1.14-1.41; P < .001) but not with all-cause mortality (OR, 0.97; 95% CI, 0.82-1.14, P = .69) after adjusting for tobacco smoking, vaccination, comorbidity, diagnosis date, and demographic factors. Conclusions and Relevance: The findings of this cohort study suggest that cannabis use may be an independent risk factor for COVID-19-related complications, even after considering cigarette smoking, vaccination status, comorbidities, and other risk factors.

The economic impact of tobacco smoking and secondhand smoke exposure in Jordan: estimating the direct and indirect costs.

AIM: To quantify the economic burden associated with tobacco smoking among smokers aged 30-69 years, and second-hand smokers (SHS) aged 15-69 years in Jordan. MATERIALS AND METHODS: A prevalence-based analysis was conducted in alignment with the Economics of Tobacco Toolkit developed by the WHO. The time-horizon of the analysis was one year (2019). Direct and indirect costs were estimated using data from the 2019 Global Burden of Diseases study. The analysis targeted the Jordanian population of smokers aged 30-69 years, and SHS aged 15-69 years. Adjustments were applied for age, gender, and smoking-related diseases. Direct costs were estimated using the smoking-attributable fraction (SAF) and national health expenditures. Indirect costs were divided into morbidity and mortality components. A discount rate of 3.0% and an annual productivity growth rate of 1.0% were assumed in modelling future economic losses. A sensitivity analysis was conducted on the lower and upper estimates of data used in this study. RESULTS: The cost of tobacco smoking and SHS exposure was estimated at US$2,108 million (95% confidence interval [CI] = US$2,003 million-US$2,245 million). This represents 4.7% (95%CI = 4.5%-5.0%) of national gross domestic product (GDP). Direct costs accounted for 3.1% of national GDP. Tobacco smoking accounted for 85.0% of total cost and SHS exposure accounted for 15.0% of total cost. Direct costs accounted for 67.0% of total cost, while indirect morbidity and mortality costs accounted for 9.0% and 24.0% of total cost, respectively. Non-communicable diseases accounted for 96.0% of total direct costs compared to communicable diseases (4.0% of total direct costs). CONCLUSIONS: Smoking cessation interventions such as raising taxes on cigarettes, protecting people from tobacco smoke, warning labels, plain packaging, and bans on advertising, are crucial for controlling national expenditures for treating smoking-related diseases and for averting future economic losses.

In this work, we aimed to calculate the annual economic impact of tobacco smoking in Jordan in 2019. We used the World Health Organization toolkit methodology to estimate both the direct and indirect costs associated with smoking nationally. Our focus was on Jordanian smokers aged 30-69 years and people exposed to second-hand smoke aged 15­69 years. Direct costs were calculated using epidemiological data on the proportion of health expenditures attributable to smoking and the national health expenditures. Indirect costs were divided into two components: morbidity and mortality. We also projected future economic losses, assuming a 3.0% discount rate and a 1.0% annual growth rate of productivity. Our study estimated that the cost of smoking and exposure to second-hand smoke was US$2,108 million (US$2,003 million-US$2,245 million), which accounted for 4.7% (4.5%-5.0) of Jordan's gross domestic product. The majority of the cost (85.0%) was due to direct smoking, while 15.0% was due to exposure to second-hand smoke. Direct costs made up 67.0% of the total cost, while the costs related to morbidity and mortality accounted for 9.0% and 24.0% of the total cost, respectively. In conclusion, our study emphasized that tobacco smoking has a significant economic impact on Jordan. Therefore, it is crucial to implement effective smoking cessation programs, such as enforcing existing anti-tobacco policies and raising taxes. These measures can help control national expenditures for treating smoking-related diseases and prevent future economic losses.

Genetic and early life factors influence on time-to-multiple sclerosis diagnosis: A UK Biobank study.

BACKGROUND: Previous investigations into multiple sclerosis (MS) risk factors predominantly relied on retrospective studies, which do not consider different follow-up times and assume a constant risk effect throughout lifetime. OBJECTIVE: We aimed to evaluate the impact of genetic and early life factors on MS diagnosis by employing a time-to-event analysis in a prospective cohort. METHODS: We used the UK Biobank data, considering the observation period from birth up to 31 December 2022. We considered genetic risk, using a multiple sclerosis polygenic risk score (MS-PRS), and various early life factors. Tobacco smoking and infectious mononucleosis diagnosis were also considered as time-varying variables along the follow-up. Using a Cox proportional hazards model, we examined the associations between these factors and MS diagnosis instantaneous risk. RESULTS: We analyzed 345,027 participants, of which 1669 had an MS diagnosis. Our analysis revealed age-dependent effects for sex (females vs males) and higher MS-PRS, with greater hazard ratios observed in young adults. CONCLUSION: The age-dependent effects suggest that retrospective studies could have underestimated sex and genetic variants' risk roles during younger ages. Therefore, we emphasize the importance of a time-to-event approach using longitudinal data to better characterize age-dependent risk effects.