Tobacco Smoking or Nicotine Phenotype and Severity of Clinical Presentation at the Emergency Department (SMOPHED): Protocol for a Noninterventional Observational Study.

BACKGROUND: In the last few years, several nicotine products have become available as alternatives to smoking tobacco. While laboratory and limited clinical studies suggest that these devices are less toxic compared to classic tobacco cigarettes, very little is known about their epidemiological impact. Visiting the emergency department (ED) often represents the first or even the only contact of patients with the health care system. Therefore, a study conducted at the ED to assess the impact of these products on health can be reliable and reflect a real-life setting. OBJECTIVE: The aim of this noninterventional observational study (SMOPHED study) is to analyze the association between the severity of clinical presentation observed during ED visits among patients using various nicotine products and the subsequent outcomes, specifically hospitalization and mortality. METHODS: Outcomes (hospitalization and mortality in the ED) will be examined in relation to various patterns of nicotine products use. We plan to enroll approximately 2000 participants during triage at the ED. These individuals will be characterized based on their patterns of tobacco and nicotine consumption, identified through a specific questionnaire. This categorization will allow for a detailed analysis of how different usage patterns of nicotine products correlate with the clinical diagnosis made during the ED visits and the consequent outcomes. RESULTS: Enrollment into the study started in March 2024. We enrolled a total of 901 participants in 1 month (approximately 300 potential participants did not provide the informed consent to participate). The data will be analyzed by a statistician as soon as the database is completed. Full data will be published by December 2024. CONCLUSIONS: There is substantial debate about the harm reduction potential of alternative nicotine products in terms of their smoking-cessation and risk-reduction potential. This study represents an opportunity to document epidemiological data on the link between the use of different types of nicotine products and disease diagnosis and severity during an ED visit, and thus evaluate the harm reduction potential claims for these products. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/54041.

Perceptions and attitudes of people with severe mental disorders towards smoking in Greece.

Despite its significant decline in the general population, smoking remains endemic and highly prevalent among people with mental disorders. The impact of smoking-attributable morbidity on life expectancy is significant since, in comparison to the general population, people with severe mental disorders have a 15-20-year reduction in life expectancy. A cross-sectional study was conducted among 1015 people with mental disorders through personal interviews. The questionnaire was designed to examine these patients' knowledge, perceptions, and attitudes towards smoking. Individuals were recruited from the mental health residential community services, the outpatient department, and the inpatient facilities of the Psychiatric Hospital of Attica. Statistical analysis was performed using SPSS 26.0. In the sample analyzed, the current-smoking prevalence stood at 68.4% (n=643), while 12.3% reported being former smokers. A staggering 86.3% smoked their first cigarette within 30 minutes of waking up, indicating a high level of dependence. Most of the former smokers (83.6%) reported that their main reason for quitting smoking was to improve their health, and the overwhelming majority (97.4%) had done so using no smoking cessation aid. Although slightly over half of the participants (53.7%) believed that health professionals adequately inform smokers about the harmful health effects of tobacco products, the information provided by health professionals on smoking cessation programs and tobacco harm reduction alternatives was considered sufficient by a mere 11.2%. Multiple logistic regression analysis demonstrated that outpatients tended to have a greater likelihood of being current smokers as compared to inpatients (OR=1.45), while users of mental health residential community services showed a significantly lower likelihood of being current smokers in comparison to inpatients (OR=0.49). Additionally, it was found that women had a lower likelihood of being current smokers compared to men (OR=0.51), while divorced/ widowed participants had a greater likelihood of being current smokers compared to single ones (OR=1.93). Finally, multiple regression analysis indicated that participants with psychotic disorders displayed a 2.39 times greater likelihood of being current smokers compared to those with mood disorders (OR=2.39). Understanding the knowledge, beliefs, and attitudes of people with mental disorders towards tobacco is an essential first step to confronting this neglected epidemic.

Patterns of flavored e-cigarette use among adult vapers in the USA: an online cross-sectional survey of 69,233 participants.

BACKGROUND: Flavored e-cigarettes remain a controversial topic with regulators planning or already implementing restrictions worldwide. In this study, we examined patterns of flavor use in e-cigarettes among a convenience sample of US adult vapers. METHODS: Participants aged ≥ 18 years who reported ever using an e-cigarette were included in the study (N = 69,233) and responded to an online questionnaire. Their smoking status was recorded as well as patterns of flavor use at e-cigarette use initiation, at the time of the survey and at the time of smoking cessation (for participants who used to smoke and were using e-cigarettes at the time of quitting). RESULTS: The most popular flavors at e-cigarette use initiation were fruit (82.8%), followed by dessert/pastry/bakery (68.6%) and candy/chocolate/sweet (52.2%). Slightly higher prevalence of using fruit and dessert/pastry/bakery flavors was observed in those who never smoked compared to those who were currently and formerly smoking. Tobacco flavors were used by 20.8% of the participants and was by far the least prevalent among participants who never smoked. Similar patterns were observed with participants' choices at the time of the survey, but tobacco flavor use was substantially reduced (7.7%). Only 2.1% reported tobacco as the single most often used flavor. The most prevalent flavor at the time of quitting smoking was again fruit (83.3%), followed by dessert/pastry/bakery (68.0%) and candy/chocolate/sweet (44.5%). These flavors were considered the most helpful for quitting smoking. Tobacco flavor use at the time of smoking cessation was reported by 15.0%, while 9.3% considered it helpful for quitting smoking. CONCLUSION: Non-tobacco flavors were popular among the US adult vapers who participated in the study, and were popular choices at the time of quitting smoking for those who formerly smoked. Tobacco flavor use prevalence was low and was further reduced over time. Regulators should consider the flavor choice of adult consumers, especially those who quit smoking, when preparing legislation on flavored e-cigarettes.

The impact of COVID-19 lockdown on children's and adolescents' mental health in Greece.

The aim of the study was to investigate the impact of the COVID-19 lockdown on children's and adolescents' mental health in Greece during the lockdown of spring 2020. A cross-sectional survey of 1232 Greek parents was conducted in spring 2020. 35.1% of parents reported that their children's psychological health was significantly affected. Parental unemployment, limited opportunity for tele-work and deteriorating psychological health, increased family conflicts and children's pre-existing physical health conditions were all significantly associated with mental health impact. Children and adolescents may experience adverse mental health effects due to the COVID-19 pandemic.

Immune response (IgG) following full inoculation with BNT162b2 COVID­19 mRNA among healthcare professionals.

Soon after the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) pandemic in December, 2019, numerous research teams, assisted by vast capital investments, achieved vaccine development in a fraction of time. However, almost 8 months following the initiation of the European vaccination programme, the need for prospective monitoring of the vaccine­induced immune response, its determinants and related side­effects remains a priority. The present study aimed to quantify the immune response following full vaccination with the BNT162b2 coronavirus disease 2019 (COVID­19) mRNA vaccine by measuring the levels of immunoglobulin G (IgG) titers in healthcare professionals. Moreover, common side­effects and factors associated with IgG titers were identified. For this purpose, blood samples from 517 individuals were obtained and analysed. Blood sampling was performed at a mean period of 69.0±23.5 days following the second dose of the vaccine. SARS­CoV­2 IgG titers had an overall mean value of 4.23±2.76. Females had higher titers than males (4.44±2.70 and 3.89 ±2.84, respectively; P=0.007), while non­smokers had higher titers than smokers (4.48±2.79 and 3.80±2.64, respectively; P=0.003). An older age was also associated with lower antibody titers (P<0.001). Moreover, the six most prevalent adverse effects were pain at the injection site (72.1%), generalized fatigue (40.5%), malaise (36.3%), myalgia (31,0%), headache (25.8%) and dizziness/weakness (21.6%). The present study demonstrated that the immune response after receiving the BNT162b2 COVID­19 mRNA vaccine is dependent on various modifiable and non­modifiable factors. Overall, the findings of the present study highlight two key aspects of the vaccination programs: First, the need for prospective immunosurveillance studies in order to estimate the duration of immunity, and second, the need to identify those individuals who are at a greater risk of developing low IgG titers in order to evaluate the need for a third dose of the vaccine.

Is SARS-CoV-2 Spike glycoprotein impairing macrophage function via α7-nicotinic acetylcholine receptors?

The innate immune cells play an important role in handling early infections, and can eliminate them completely up to a certain threshold. Beyond that threshold they take up their role in "The Resolution of Inflammation". The recognition of the SARS-CoV-2 antigen triggers an eicosanoid storm and initiates a robust inflammatory response. This establishes a positive feedback loop which develops into a sustained cytokine storm which interferes with the activation of adaptive immune cells. The mechanism of this interaction, and hence the pathogenesis of the virus with the immune system, is yet to be determined. In silico studies predict a direct SARS-CoV-2 spike glycoprotein interaction with nicotinic acetylcholine receptors, which could impair macrophage function and initiate the cascade of events in severe infections. We here, add to the hypothesis that immune dysregulation can be caused by the interaction of the SARS-CoV-2 spike glycoprotein via a cryptic epitope with the α7-nAChR in Type-1 macrophages, discuss its implications for the treatment of COVID-19 patients, and present better prospects for the design and dissemination of more effective vaccines and their importance.

Nicotinic cholinergic system and COVID-19: In silico evaluation of nicotinic acetylcholine receptor agonists as potential therapeutic interventions.

SARS-CoV-2 infection was announced as a pandemic in March 2020. Since then, several scientists have focused on the low prevalence of smokers among hospitalized COVID-19 patients. These findings led to our hypothesis that the Nicotinic Cholinergic System (NCS) plays a crucial role in the manifestation of COVID-19 and its severe symptoms. Molecular modeling revealed that the SARS-CoV-2 Spike glycoprotein might bind to nicotinic acetylcholine receptors (nAChRs) through a cryptic epitope homologous to snake toxins, substrates well documented and known for their affinity to the nAChRs. This binding model could provide logical explanations for the acute inflammatory disorder in patients with COVID-19, which may be linked to severe dysregulation of NCS. In this study, we present a series of complexes with cholinergic agonists that can potentially prevent SARS-CoV-2 Spike glycoprotein from binding to nAChRs, avoiding dysregulation of the NCS and moderating the symptoms and clinical manifestations of COVID-19. If our hypothesis is verified by in vitro and in vivo studies, repurposing agents currently approved for smoking cessation and neurological conditions could provide the scientific community with a therapeutic option in severe COVID-19.

Nicotinic cholinergic system and COVID-19: In silico identification of interactions between α7 nicotinic acetylcholine receptor and the cryptic epitopes of SARS-Co-V and SARS-CoV-2 Spike glycoproteins.

SARS-CoV-2 is the coronavirus that originated in Wuhan in December 2019 and has spread globally. Studies have shown that smokers are less likely to be diagnosed with or be hospitalized for COVID-19 but, once hospitalized, have higher odds for an adverse outcome. We have previously presented the potential interaction between SARS-CoV-2 Spike glycoprotein and nicotinic acetylcholine receptors (nAChRs), due to a "toxin-like" epitope on the Spike glycoprotein, with homology to a sequence of a snake venom toxin. This epitope coincides with the well-described cryptic epitope for the human anti-SARS-CoV antibody CR3022. In this study, we present the molecular complexes of both SARS-CoV and SARS-CoV-2 Spike glycoproteins, at their open or closed conformations, with the model of the human α7 nAChR. We found that all studied protein complexes' interface involves a large part of the "toxin-like" sequences of SARS-CoV and SARS-CoV-2 Spike glycoproteins and toxin binding site of human α7 nAChR. Our findings provide further support to the hypothesis about the protective role of nicotine and other cholinergic agonists. The potential therapeutic role of CR3022 and other similar monoclonal antibodies with increased affinity for SARS-CoV-2 Spike glycoprotein against the clinical effects originating from the dysregulated cholinergic pathway should be further explored.

Smoking prevalence among hospitalized COVID-19 patients and its association with disease severity and mortality: an expanded re-analysis of a recent publication.

BACKGROUND: There is a lot of debate about the effects of smoking on COVID-19. A recent fixed-effects meta-analysis found smoking to be associated with disease severity among hospitalized patients, but other studies report an unusually low prevalence of smoking among hospitalized patients. The purpose of this study was to expand the analysis by calculating the prevalence odds ratio (POR) of smoking among hospitalized COVID-19 patients, while the association between smoking and disease severity and mortality was examined by random-effects meta-analyses considering the highly heterogeneous study populations. METHODS: The same studies as examined in the previous meta-analysis were analyzed (N = 22, 20 studies from China and 2 from USA). The POR relative to the expected smoking prevalence was calculated using gender and age-adjusted population smoking rates. Random-effects meta-analyses were used for all other associations. RESULTS: A total of 7162 patients were included, with 482 being smokers. The POR was 0.24 (95%CI 0.19-0.30). Unlike the original study, the association between smoking and disease severity was not statistically significant using random-effects meta-analysis (OR 1.40, 95%CI 0.98-1.98). In agreement with the original study, no statistically significant association was found between smoking and mortality (OR 1.86, 95%CI 0.88-3.94). CONCLUSION: An unusually low prevalence of smoking, approximately 1/4th the expected prevalence, was observed among hospitalized COVID-19 patients. Any association between smoking and COVID-19 severity cannot be generalized but should refer to the seemingly low proportion of smokers who develop severe COVID-19 that requires hospitalization. Smokers should be advised to quit due to long-term health risks, but pharmaceutical nicotine or other nicotinic cholinergic agonists should be explored as potential therapeutic options, based on a recently presented hypothesis.

Association between electronic cigarette use and smoking cessation in the European Union in 2017: analysis of a representative sample of 13 057 Europeans from 28 countries.

OBJECTIVES: To examine the association between electronic cigarette (e-cigarette) use and smoking cessation in the European Union (EU) in 2017 according to e-cigarette use frequency and smoking cessation duration. DESIGN: Cross-sectional survey of EU citizens, representative of the population (Special Eurobarometer 458). Weighted proportions (95% CI) and adjusted prevalence ratios (aPRs) were calculated. SETTING: EU. PARTICIPANTS: 13 057 EU citizens aged ≥15 years (6904 current and 6153 former smokers). RESULTS: Current daily e-cigarette use was reported by 2.4% (1.8%-3.1%) of current and 3.3% (2.5%-4.2%) of former smokers (p=0.002), while former daily use was reported by 5.6% (4.7%-6.8%) and 1.9% (1.3%-2.7%), respectively (p<0.001). More than half of all former smokers had quit for >10 years. Current daily e-cigarette use was rare among former smokers of >10 years (0.2%, 0.1%-0.6%) and was more prevalent in former smokers of ≤2 and 3-5 years (12.9%, 9.1%-17.9% and 9.0%, 5.8%-13.7%, respectively). Compared with never use, current daily e-cigarette use was associated with being a former smoker of ≤2 (aPR 4.96, 95% CI 3.57 to 6.90) and 3-5 years (aPR 3.20, 95% CI 2.10 to 4.87). Former daily e-cigarette use was associated with being a former smoker of ≤2 years (aPR 1.96, 95% CI 1.21 to 3.12). Current daily e-cigarette use was negatively associated with being a former smoker of 5-10 and >10 years. CONCLUSIONS: Current daily e-cigarette use in the EU in 2017 was rare among former smokers of >10 years and was positively associated with recent (≤5 years) smoking cessation. Former daily e-cigarette use was also positively associated with recent (≤2 years) smoking cessation.

Changes from 2017 to 2018 in e-cigarette use and in ever marijuana use with e-cigarettes among US adolescents: analysis of the National Youth Tobacco Survey.

AIMS: To examine changes from 2017 to 2018 in e-cigarette use and ever marijuana use with e-cigarettes among US adolescents. DESIGN: Analysis of data from the 2017 and 2018 National Youth Tobacco Survey (NYTS), cross-sectional surveys of US middle school (grades 6-8) and high school (grades 9-12) students. SETTING: United States. PARTICIPANTS: US adolescent population from middle school, with mean age = 12.7 [standard deviation (SD) = 1.0] years, and high school, with mean age = 16.1 (SD = 1.3) years. MEASUREMENTS: Analysis of e-cigarette use and ever use of marijuana with e-cigarettes according to frequency of use and smoking status, comparing 2017 with 2018. Frequent smoking and e-cigarette use was defined as use for ≥ 20 of the past 30 days. FINDINGS: Past 30 days e-cigarette use was reported by 33.1% [95% confidence interval (CI) = 29.1-37.4%] of ever/no past 30 days smokers, 68.6% (95% CI = 64.1-72.7%) of past 30 days smokers and 7.2% (95% CI = 6.3-8.2%) of never smokers in 2018 and by 19.3% (95% CI = 16.1-23.1%), 53.0% (95% CI = 46.9-58.9%) and 3.3% (95% CI = 2.7-4.4%) in 2017, respectively (all P < 0.001). Prevalence of past 30 days e-cigarette use was higher among frequent smokers (69.8%, 95% CI = 62.3-76.5% in 2018; 53.8%, 95% CI = 44.1-63.2% in 2017, P < 0.001) and lower among never smokers. Most of the latter were infrequent users, while frequent and daily e-cigarette use was 18- and 24-fold lower compared with ever smokers, respectively. Approximately half of past 30 days and 70% of frequent e-cigarette users reported ever marijuana use with e-cigarettes in both years. Past 30 days smokers were more likely to report past 30 days e-cigarette use [odds ratio (OR) = 15.79, 95% CI = 12.58-19.83 in 2018; OR = 16.11, 95% CI = 12.44-20.86 in 2017) compared with adolescents reporting no past 30 days smoking. CONCLUSIONS: Among US adolescents, e-cigarette use increased in all smoking groups in 2018 compared with 2017. Frequent and daily e-cigarette use was far lower in never-smokers compared with ever-smokers. High prevalence of ever marijuana use with e-cigarettes was observed.

Improved strategies to counter the COVID-19 pandemic: Lockdowns vs. primary and community healthcare.

COVID-19 pandemic mitigation strategies are mainly based on social distancing measures and healthcare system reinforcement. However, many countries in Europe and elsewhere implemented strict, horizontal lockdowns because of extensive viral spread in the community which challenges the capacity of the healthcare systems. However, strict lockdowns have various untintended adverse social, economic and health effects, which have yet to be fully elucidated, and have not been considered in models examining the effects of various mitigation measures. Unlike commonly suggested, the dilemma is not about health vs wealth because the economic devastation of long-lasting lockdowns will definitely have adverse health effects in the population. Furthermore, they cannot provide a lasting solution in pandemic containment, potentially resulting in a vicious cycle of consecutive lockdowns with in-between breaks. Hospital preparedness has been the main strategy used by governments. However, a major characteristic of the COVID-19 pandemic is the rapid viral transmission in populations with no immunity. Thus, even the best hospital system could not cope with the demand. Primary, community and home care are the only viable strategies that could achieve the goal of pandemic mitigation. We present the case example of Greece, a country which followed a strategy focused on hospital preparedness but failed to reinforce primary and community care. This, along with strategic mistakes in epidemiological surveillance, resulted in Greece implementing a second strict, horizontal lockdown and having one of the highest COVID-19 death rates in Europe during the second wave. We provide recommendations for measures that will reinstate primary and community care at the forefront in managing the current public health crisis by protecting hospitals from unnecessary admissions, providing primary and secondary prevention services in relation to COVID-19 and maintaining population health through treatment of non-COVID-19 conditions. This, together with more selective social distancing measures (instead of horizontal lockdowns), represents the only viable and realistic long-term strategy for COVID-19 pandemic mitigation.

Combined Toxicity of Cannabidiol Oil with Three Bio-Pesticides against Adults of Sitophilus Zeamais, Rhyzopertha Dominica, Prostephanus Truncatus and Trogoderma Granarium.

The present study investigates the interaction between cannabidiol (CBD) oil and three biopesticides: Azatin and two baculovirus formulations (Madex and Helicovex), both separately and in combination, in order to investigate their interaction against adults of four major coleopteran stored-product pests: Sitophilus zeamais (Coleoptera: Curculionidae), Rhyzopertha dominica (Coleoptera: Bostrichidae), Prostephanus truncatus (Coleoptera: Bostrichidae) and Trogoderma granarium (Coleoptera: Dermestidae). CBD, which has been understudied for its insecticidal properties, was applied at three different doses (500, 1500 and 3000 ppm). The biopesticides were administered at 1500 ppm. Interactions in the combined treatments were mathematically estimated as not synergistic and mostly competitive except for the combined treatments of CBD (1500 and 3000 ppm) with Azatin (1500 ppm) which were marked by an additive interaction. In its individual application, CBD oil generated the highest insect mortality while its effect was clearly dose-dependent. The findings reveal a promising effect of CBD oil against these coleopterans which had not been previously tested together.

Imiquimod - A toll like receptor 7 agonist - Is an ideal option for management of COVID 19.

According to numerous recent publications, the COVID-19 patients have lymphopenia, higher infection-related biomarkers and several elevated inflammatory cytokines (i.e. tumor necrosis factor (TNF)-α, interleukin IL-2R and IL-6). The total number of B cells, T cells and NK cells are significantly decreased. RNA viruses, SARS-CoV-2 included, hit the innate immune system in order to cause infection, through TLRs 3, 7 and 8. Imiquimod is an immune-stimulator that activates TLR 7 and can be used to enhance the innate and adaptive immunity. Preclinical and clinical trials are proposed.