Past, Present, and Future Diagnostic Methods for the Early Noninvasive Detection of Oral Premalignant Lesions: A State of the Art and Systematic Review.

Objectives: To provide an in-depth analysis of noninvasive methods for the early diagnosis of oral premalignant lesions, focusing on novel biomarkers and optical technologies, and to discuss their potential in improving the prognosis of patients with oral oncological diseases. Methods: This state-of-the-art review examines various noninvasive diagnostic techniques, including the utilization of salivary microRNAs and optical technologies such as Raman spectroscopy, elastic scattering spectroscopy, diffuse reflectance spectroscopy, narrow-band imaging, autofluorescence imaging, toluidine blue staining, and microendoscopy. Results: Several noninvasive techniques have shown varying degrees of effectiveness in detecting oral cancer. Autofluorescence imaging exhibited sensitivities up to 100% but had variable specificity. toluidine blue staining reported sensitivity between 77% and 100% for high-risk lesions or cancer, with specificity around 45% to 67%. Spectroscopy techniques achieved 72% to 100% sensitivities and specificities of 75% to 98%. Microendoscopy presented a sensitivity of 84% to 95% and a specificity of 91% to 95%. Conclusion: The review highlights the strengths and limitations of each noninvasive diagnostic method and their recent advancements. Although promising results have been demonstrated, there is a need for further development of reliable strategies for early detection and intervention in oral oncology.

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.

Behavioral Therapy for People With Diabetes Who Smoke: A Scoping Review.

BACKGROUND: Tobacco smoking exacerbates diabetes-related complications; its prevalence is notwithstanding substantial. Persons with diabetes face a number of barriers and challenges to quitting such as multiple lifestyle restrictions; tailored interventions are required for smoking cessation. OBJECTIVE: To identify research on behavioral interventions for smoking cessation in diabetes. METHODS: Studies had to be randomized controlled trials, quasiexperimental or systematic reviews. The behavioral interventions included were: the 5As, Cognitive-Behavioral Therapy, Motivational Interviewing, Contingency Management, Health Coaching and Counselling, as compared to standard care. The outcomes were self-reported and/or biochemically verified smoking cessation. CINAHL Complete, MEDLINE Complete, the Cochrane databases of systematic reviews and randomized controlled trials, PsychInfo and PubMed Central were searched until July, 2023. Keywords used included diabetes, smoking cessation and each of the behavioral interventions included. RESULTS: 1615 papers were identified. Three studies on the 5As/brief advice, 4 on Motivational Intervention and 1 on counseling were retained. The results on the 5As and Motivational Interviewing were conflicting. More intensive interventions appear to be more successful in achieving smoking cessation in smokers with diabetes. CONCLUSIONS: Future research should focus on the continued development and evaluation of structured smoking cessation interventions based on the 5As, Motivational interviewing and Cognitive Behavioral Therapy.

Protocol for the "magnitude of cigarette substitution after initiation of e-cigarettes and its impact on biomarkers of exposure and potential harm in dual users" (MAGNIFICAT) study.

Introduction: Many smokers who use e-cigarettes (ECs) to quit continue smoking alongside vaping. The impact on health among individuals who simultaneously smoke conventional cigarettes (CCs) and use ECs remains unclear. The varying patterns of dual use present differing levels of overall toxin exposure and relative risks concerning smoking-related diseases. Understanding these complexities is vital to assessing the implications for human health. Objective: Herein we describe a protocol designed to analyze the impact of different level of substituting CCs with ECs on exposure to toxicants. We'll use biomarkers to measure this exposure and assess harm reduction in dual users through clinical endpoints, harm-related biomarkers, and behavioral correlations. We expect to observe progressive changes with varying patterns of dual use. Methods and analyses: For this purpose, we planned to recruit a group of 250 smokers who will be asked to reduce their CC consumption by adopting ECs (intervention group). A separate group of 50 smokers will continue to smoke CC (reference group). Study groups will be followed up for 6 months during which biospecimens will be collected for biomarker analyses, and clinical endpoints will be assessed. The trial is structured to characterize subjects' usage patterns over time using robust biomarkers of exposure and a standardized mobile phone application to facilitate the precise categorization of dual users along the risk continuum based on their usage behaviors. Subject recruitment will start in February 2024 and enrolment is expected to be completed by August 2024. Results will be reported early in 2025. Study findings may provide valuable insights into health benefits or risks associated with varying patterns of dual use. Ethics and dissemination: The study protocol and informed consent forms will be approved by the local Ethical Review Boards. Study results will be disseminated through articles published in reputable, peer-reviewed, open access, scientific journals, presentations at conferences, and the University website.

Effects of Electronic Nicotine Delivery Systems Substitution on Body Weight Status: Protocol for a Systematic Review and Meta-Analysis.

BACKGROUND: Weight gain following smoking cessation is a well-documented concern, often attributed to the absence of nicotine's metabolic influence. The adoption of Electronic Nicotine Delivery Systems (ENDS) has been used to achieve smoking cessation, with claims of aiding weight control. However, existing reviews present conflicting conclusions on ENDS' impact on weight status, necessitating a rigorous evaluation. OBJECTIVE: We aim to conduct a systematic review with meta-analysis to assess the actual impact of ENDS on weight status in individuals who have ceased or reduced conventional smoking. The primary goal is to provide clinicians with evidence-based insights into the potential effects of ENDS use as a smoking substitute on weight control. METHODS: Adhering to PRISMA-P (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols) guidelines, our systematic review will analyze randomized and nonrandomized controlled trials, clinical trials (quasi-experimental), and prospective or retrospective cohort studies on the weight status effects of ENDS among individuals who have either quit or reduced smoking. Searches will include PubMed, Scopus, and Cochrane Library, covering the period from 2010 to January 2024. A gray literature search and supplementary searches will be performed. Data will be extracted independently by 2 reviewers and quality assessments will be conducted concurrently. Quality assessments will use Joanna Briggs Institute tools, 2020 version, along with bias assessments for internal validity and reporting bias based on the Catalogue of Bias. The included studies will be examined for any internal data reporting discrepancies by using Puljak's checklist. Meta-analysis and subgroup analyses (ie, general ENDS usage, ENDS use coupled with a reduction in smoking exceeding 50%, and exclusive ENDS use for achieving smoking cessation) are planned. Certainty of evidence will be evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. RESULTS: The protocol has been registered in PROSPERO (CRD42023494974) and the entire systematic review is expected to be completed by April 2024. The main goal of this review is to retrieve all current human research studies investigating the influence of ENDS on weight management among individuals who have quit or reduced smoking. Furthermore, the review will assess the quality of these studies and examine potential biases to identify the most dependable evidence available. Dissemination strategies will include traditional journal publications, social media announcements, and a white paper. The latter, available for download and distributed at conferences, aims to reach a broad audience, including clinicians and ENDS users. CONCLUSIONS: The review will address the importance of informing health care professionals and patients about the current and robust evidence regarding the effects of transitioning to ENDS for smoking cessation on weight status. TRIAL REGISTRATION: PROSPERO CRD42023494974; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=494974. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/56324.

A Global Health Survey of People Who Vape but Never Smoked: Protocol for the VERITAS (Vaping Effects: Real-World International Surveillance) Study.

BACKGROUND: There is only limited information about the health effects of regular vaping. Research on the health status of people who used to smoke faces the challenge that previous smoking may have caused unknown health effects. Only studies of people who vape but have never smoked combustible cigarettes can enable the detection of harms attributable to vaping. Large prospective studies of well-characterized electronic cigarette users with and without a history of combustible cigarette smoking are warranted to establish the long-term effects of regular vaping on respiratory health. OBJECTIVE: We will conduct a global cross-sectional survey of individuals from 6 world regions. Respiratory symptoms will be assessed using a validated questionnaire-the Respiratory Symptom Experience Scale (RSES). Current vapers who are nonusers of other tobacco or nicotine products will be compared with matched controls who are nonusers of vapes and other tobacco or nicotine products. METHODS: This will be a multicountry, cross-sectional internet-based survey of 750 adults aged ≥18 years who satisfy the criteria for inclusion in either a cohort of people who exclusively vape and who are nonusers of other tobacco or nicotine products ("vapers cohort"; target N=500) or a cohort of nonvapers who are also nonusers of other tobacco or nicotine products ("controls cohort"; target N=250). The primary end point of the study is the RSES score. RSES scores of people in the "vapers cohort" will be compared with those of people in the "controls cohort." Additionally, the study will collect data to characterize patterns of vaping product use among the vapers cohort. Data collection will include information about the age initiation of using vape products, reasons for starting and continuing the use of vape products, specific types of products used, flavors and nicotine strengths of recently used products, as well as the frequency and intensity of product use in the past 30 days. RESULTS: Participant recruitment started in April 2023, and enrollment was completed by November 2023 with 748 participants. Results will be reported in 2024. CONCLUSIONS: This will be the first study providing key insights into respiratory health effects associated with using electronic cigarettes in people who vape with no established use of combustible cigarettes or other tobacco or nicotine products. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/54236.

Changes in Oral Health and Dental Esthetic in Smokers Switching to Combustion-Free Nicotine Alternatives: Protocol for a Multicenter and Prospective Randomized Controlled Trial.

BACKGROUND: Although the detrimental effects of conventional combustible cigarettes on oral health and dental esthetics are well known, there is limited information about the long-term impact of combustion-free nicotine alternatives (C-F NA) such as e-cigarettes or heated tobacco products. OBJECTIVE: This multicenter, prospective, 3-parallel-arm randomized controlled trial will investigate whether switching from combustible cigarettes to C-F NA will lead to measurable improvements in oral health parameters and dental esthetics over 18 months in adult smokers with limited gum disease. METHODS: Regular smokers not intending to quit and without clinical signs of periodontitis will be randomly assigned (1:4 ratio) to either standard of care with brief cessation advice (control group; arm A) or C-F NA use (intervention group; arm B). The study will also include a reference group of never smokers (reference group; arm C). The primary end point is the change in the Modified Gingival Index (MGI) score from baseline between the control arm (arm A) and the intervention arm (arm B) at the 18-month follow-up. In addition, the study will analyze the within- and between-group (arms A, B, and C) changes in MGI assessment, plaque imaging, dental shade quantitation, tooth stain scores, and oral health-related quality of life questionnaires measured at each study time point. All participants will attend a total of 7 clinic visits: screening, enrollment, and randomization (visit 0); baseline visit-day 14 (visit 1); day 90 (visit 2); day 180 (visit 3); day 360 (visit 4); and day 540 (visit 5). This multicenter study will be conducted in 4 dental clinics in 4 countries. The statistical analysis will involve descriptive statistics for continuous and categorical data. Primary end points will undergo tests for normality and, based on distribution, either a 2-sided t test or Mann-Whitney U test. Linear mixed model with random factors center and study arms by center will also be applied. Secondary end points, including MGI assessment and quality of life, will be subjected to similar tests and comparisons. Only if one value of the parameter MGI is missing after day 1, the last available observation will be carried forward. The analysis will be performed on the substituted data. Secondary parameters will not have missing value replacement. RESULTS: Participant recruitment began in October 2021, and enrollment was completed in June 2023. Results will be reported in 2025. CONCLUSIONS: This will be the first study to provide key insights into oral health benefits or risks associated with using C-F NA in smokers who are seeking alternatives to cigarette smoking. TRIAL REGISTRATION: ClinicalTrials.gov NCT04649645; https://clinicaltrials.gov/ct2/show/NCT04649645. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/53222.

A multicenter prospective randomized controlled trial investigating the effects of combustion-free nicotine alternatives on cardiovascular risk factors and metabolic parameters in individuals with type 2 diabetes who smoke: the DiaSmokeFree study protocol.

Stopping smoking is crucial for public health and especially for individuals with diabetes. Combustion-free nicotine alternatives like e-cigarettes and heated tobacco products are increasingly being used as substitutes for conventional cigarettes, contributing to the decline in smoking prevalence. However, there is limited information about the long-term health impact of those products in patients with diabetes. This randomized controlled trial aims to investigate whether switching from conventional cigarettes to combustion-free nicotine alternatives will lead to a measurable improvement in cardiovascular risk factors and metabolic parameters over a period of 2 years in smokers with type 2 diabetes. The multicenter study will be conducted in seven sites across four countries. A total of 576 smokers with type 2 diabetes will be randomly assigned (1:2 ratio) to either standard of care with brief cessation advice (Control Arm) or combustion-free nicotine alternatives use (Intervention Arm). The primary end point is the change in the proportion of patients with metabolic syndrome between baseline and the 2-year follow-up. Additionally, the study will analyze the absolute change in the sum of the individual factors of metabolic syndrome at each study time point. Patient recruitment has started in September 2021 and enrollment is expected to be completed by December 2023. Results will be reported in 2026. This study may provide valuable insights into cardiovascular and metabolic health benefits or risks associated with using combustion-free nicotine alternatives for individuals with type 2 diabetes who are seeking alternatives to tobacco cigarette smoking. The study protocol, informed consent forms, and relevant documents were approved by seven ethical review boards. Study results will be disseminated through articles published in high-quality, peer-reviewed journals and presentations at conferences.

Correction: Carota et al. Neuroprotective Role of α-Lipoic Acid in Iron-Overload-Mediated Toxicity and Inflammation in In Vitro and In Vivo Models. Antioxidants 2022, 11, 1596.

In the original publication [...].

User evaluation and feasibility test of an app designed for smoking cessation in Italian people who smoke: preliminary findings from an uncontrolled pre-test post-test open study.

BACKGROUND: mHealth is a public health practice that exploits the use of mobile devices, including smartphone applications. We will describe an uncontrolled pre-test post-test open pilot study concerning the feasibility evaluation of a smartphone App designed to help in smoking cessation. The aim of this study is to evaluate the feasibility of a smartphone app as a tool for smoking cessation. This study is necessary to the literature because smoking is a major public health concern and has been linked to various health issues such as cardiovascular disease, respiratory disease, and cancer. While there are several smoking cessation interventions available, the use of mobile devices to aid in smoking cessation is a relatively new and innovative approach that requires further investigation. METHODS: The App "Smoke Free" was configured on the devices of N = 30 participants who smoked combustible cigarette, 13 males and 17 females aged 18 to 55 years, with the indications to use it for 90 days, describe their experience, suggest new features, and report any critical aspect. The study consisted of an initial screening visit to select participants that reflected the inclusion criteria and 4 study visits: a baseline visit, two follow-up visits, and one final visit. We used descriptive stats to summarize results. Repeated measures ANOVA and Wilcoxon test were used to test differences in smoking consumption, self-reported craving, and measured eCO level. Statistical software Jamovi was used for analysis. Interviews were conducted via phone or in-person and analyzed using qualitative description principles. RESULTS: Participants evaluated the app as having good aesthetic appeal and user-friendliness but being moderately useful, despite some quitting or reducing their smoking behavior. To improve it, participants have proposed features such as more notifications, social network integration, and damage caused by smoking to the body over time for future app updates. CONCLUSIONS: The application was moderately useful with good feasibility, with several suggestions for future updates that could improve its effectiveness.

A scoping review of new technologies for dental plaque quantitation: Benefits and limitations.

OBJECTIVES: To determine the validity and reliability of novel digitalized tools for dental plaque detection and explore the benefits and limitations connected to their use. DATA: Reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Extension for Scoping Reviews. All human clinical studies comparing dental plaque detection using digitalized systems against a standard reference were included. SOURCES: PubMed and Scopus were screened from 01 January 2013 to 28 September 2023. Bibliographies of primary studies and principal peer-reviewed scientific journals were manually searched. STUDY SELECTION: The initial search identified 576 articles, with a total of 13 included in the review, published between 2015 and 2023. Most of the studies included (77 %) were cross-sectional with three being prospective. Digital devices captured 2D and 3D images via cameras and intra-oral scanners, respectively. The Turesky's modified plaque index was the most frequent clinical index. Correlation with clinical examination was moderate to strong, with good to excellent intra- and inter-system agreement. CONCLUSIONS: Within the limitations of this scoping review, image analysis-based plaque detection systems demonstrated good correlations with clinical plaque indices, using both 2D and 3D imaging systems. Whilst digital plaque detection devices offer advantages in terms of procedural standardization and reproducibility, they also have limitations, therefore currently, their application should be underpinned by a comprehensive clinical examination. CLINICAL SIGNIFICANCE: Digital plaque detection tools, that provide standardized measurements and store acquired images, facilitate more informed feedback to patients. This objective analysis may enhance clinician confidence in their utility for clinical trials and other applications.

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.

Cytotoxicity, mutagenicity and genotoxicity of electronic cigarettes emission aerosols compared to cigarette smoke: the REPLICA project.

Concerns have recently increased that the integrity of some scientific research is questionable due to the inability to reproduce the claimed results of some experiments and thereby confirm that the original researcher's conclusions were justified. This phenomenon has been described as 'reproducibility crisis' and affects various fields from medicine to basic applied sciences. In this context, the REPLICA project aims to replicate previously conducted in vitro studies on the toxicity of cigarette smoke and e-cigarette aerosol, sometimes adding experiments or conditions where necessary, in order to verify the robustness and replicability of the data. In this work the REPLICA Team replicated biological and toxicological assessment published by Rudd and colleagues in 2020. As in the original paper, we performed Neutral Red Uptake (NRU) assay for the evaluation of cytotoxicity, Ames test for the evaluation of mutagenesis and In Vitro Micronuclei (IVMN) assay for the evaluation of genotoxicity on cells treated with cigarette smoke or e-cigarette aerosol. The results showed high cytotoxicity, mutagenicity and genotoxicity induced by cigarette smoke, but slight or no cytotoxic, mutagenic and genotoxic effects induced by the e-cigarette aerosol. Although the two studies presented some methodological differences, the findings supported those previously presented by Rudd and colleagues.

Respiratory health effects of e-cigarette substitution for tobacco cigarettes: a systematic review.

BACKGROUND: E-cigarettes (electronic nicotine delivery system, ENDS) have been presented as a harm reduction strategy for people who smoke tobacco cigarettes but who cannot achieve abstinence, or for those who wish to continue to enjoy nicotine and the habit of smoking. What are the health effects of the substitution of ENDS for tobacco cigarettes? This systematic review evaluates the evidence of human clinical tests on the respiratory effects of ENDS use in participants who smoke tobacco cigarettes. METHODS: A registered and published protocol was developed conforming to PRISMA 2020 and AMSTAR2 standards. The literature search was conducted in PubMed, Scopus, and the CENTRAL Cochrane Library and updated to May 2022. Three supplementary searches and a grey literature search were performed. Studies were evaluated with the JBI quality tools and the Oxford Catalogue of Bias. Due to the heterogeneity (diversity) of the studies, a narrative data synthesis was performed on the test findings plus three sub-group analyses. RESULTS: The review consists of sixteen studies and twenty publications. Spirometry tests comprised the majority of the data. In total, 66 respiratory test measurements were reported, out of which 43 (65%) were not significant. Statistically significant findings were mixed, with 9 tests showing improvements and 14 measuring declines, none of which was clinically relevant. Ten studies were rated at a high risk of bias, and six had some concerns primarily due to inadequate research designs and the conduct of the studies. Reporting bias was documented in thirteen studies. CONCLUSIONS: Most of the studies showed no difference in respiratory parameters. This indicates that ENDS substitution for smoking likely does not result in additional harm to respiratory health. Due to the low quality of the studies, confidence in the conclusions is rated as low. Robust studies with a longer duration and sufficient power are required to validate any potential benefits or possible harms of ENDS substitution. Registration PROSPERO #CRD42021239094, International Registered Report Identifier (IRRID): DERR1-10.2196/29084.