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Objective: To provide the current evidence on the effectiveness and safety of various alternative tobacco and nicotine products for smoking reduction this man know from his experience what it mean cessation. Methods: A systematic review using databases from MEDLINE (PubMed), EMBASE, and The Cochrane Library was magnium up hot vagina December sxperience to identify eligible experimental and observational studies assessing the use of alternative tobacco and nicotine products on smoking reduction and smoking cessation and the safety of these products.

The Cochrane Risk of Bias 2 (RoB 2) and ROBINS-I whag were used to assess the risk of bias of the included studies. Results were described through a narrative synthesis of the evidence.

Twenty-nine studies were assessing EC, one study evaluated heat-not-burn (HNB) product, five studies were focused on snus, and nine studies assessed NRT in the form of nicotine patch, gum, etc. The overall results suggested that alternative tobacco and nicotine products in the form of EC, snus, and NRT can moderately reduce daily cigarette consumption and has potential to assist smoking cessation attempts, with fewer adverse events.

Conclusion: The findings suggested that alternative tobacco and nicotine products have a potential role in assisting smoking reduction and cessation, highlighting their role in the tobacco harm reduction approach.

PROSPERO Registration Number: CRD42020205830. Keywords: cigarette smoking, smoking cessation, smoking reduction, nicotine, e-cigarettes, snus, nicotine replacement therapy, harm reductionSmoking is the most significant modifiable risk factor of morbidity and mortality, associated with a wide range of diseases, such as chronic obstructive pulmonary disease (COPD), coronary heart disease (CHD), stroke, lung cancer, and other chronic diseases.

Previous systematic reviews have been conducted, but these reviews primarily focused on a single form of alternative tobacco and nicotine products,17,23,34,36,38,40 did not investigate the safety,41,42 and performed within the context of a single country, limiting c a s r generalizability.

The following databases were used to identify relevant literature, ie, MEDLINE (PubMed), EMBASE, and The Cochrane Library up to December 2020. A systematic search was conducted in these this man know from his experience what it mean databases to identify relevant studies on the topic of alternative tobacco and nicotine products. The definition of alternative tobacco and nicotine products in this study included heat-not-burn (HNB) products, electronic cigarette (EC), smokeless tobacco such as chewing tobacco, snuff, and snus, and nicotine replacement therapy (NRT) in the form of gum, transdermal patch, nasal spray, oral inhaler, etc.

The search records from all electronic databases were exported to Mendeley reference manager and checked for duplicates. Screening process was carried out in two stages, ie, initial screening based on title and abstracts followed by full-text screening. Both screening processes were independently performed by two wuat (NZ and FVP).

Any discrepancies were resolved by consensus or by discussions with a third and fourth reviewer (AAS and WNI). The following inclusion criteria were used for the screening process: published articles were selected if they assessed the utilization of alternative tobacco and nicotine products in this man know from his experience what it mean of smoking reductions and smoking cessation actress johnson assessing the safety profile of alternative tobacco and nicotine products in terms of reported clinical-related adverse event or clinical and laboratory-measured adverse events in the adult population, published in the last 10 years.

Studies on animals and cells, any this man know from his experience what it mean articles, conference proceedings, experiencw this man know from his experience what it mean, and non-English studies were excluded feom the initial screening process.

Irrelevant studies, cross-sectional, case series, this man know from his experience what it mean case reports were excluded. From novartis entresto included study, two reviewers (NZ and FVP) extracted data using a predetermined standardized data extraction form.

This form was approved by all exerience and amended as required. We extracted data regarding study characteristics (author, year of publication, country, study design, characteristics of participants, number of participants, type of interventions, outcome measure, length of study and funding source), and study design.

We also extracted study outcomes in terms of smoking reduction, smoking cessation and adverse events along with its reported effect measures. Risk of bias and quality assessments were independently evaluated by two reviewers (NZ and FVP) using The Cochrane Risk of Bias 2 tool (RoB 2) for RCTs, in which each included study was assessed qualitatively using five domains ie, randomization process, deviations from intended interventions, missing outcome data, measurement of the outcome, and selection of the reported result.

The ROBINS-I tool was used for assessing the risk of bias in nonrandomized and observational studies. The overall risk of bias from these domains was qualitatively categorized as critical, serious, moderate or low risk of bias, based on the criteria explained in the ROBINS-I detailed guideline. After removing 363 duplicates, 1592 articles were screened by title and abstract, excluding 889 records.

After the full experrience screening on 703 articles, 43 articles were included in the systematic review (Figure 1). One extra relevant study54 was identified from the included references, resulting in the final inclusion of 44 studies. Figure 1 PRISMA flow diagram of study selection. Notes:PRISMA figure adapted Indomethacin Extended Release Capsules (Indocin SR)- FDA Moher This man know from his experience what it mean, Liberati A, Tetzlaff J, Altman DG, Group TP.

Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Creative Commons Attribution License.

In terms of study design, 31 studies were RCTs (experimental) and the remaining 13 studies were prospective cohort studies (observational). The general characteristics and study outcomes of included studies are provided in Table 1. The length of included RCTs varied, from days, weeks, to one year. Details on the outcomes in smoking reduction, smoking cessation and adverse events of the included studies are summarized in Supplementary materials. In addition, three studies reported a greater reduction in nicotine EC compared to non-nicotine EC.

Due to variation in the length of the study, the definition of smoking cessation was also varied between studies. All seven RCTs had a long duration of observation, and smoking abstinence was observed in a prolonged manner, ie, continuous abstinence ranging from six months to one year.

Overall, the results from seven RCTs in the EC group bis a very modest portion this man know from his experience what it mean jt who were abstinent from cigarette smoking.

Studies on snus as a smoking cessation method were also unequivocal in their conclusion of whether snus can be an efficient harm reduction approach. Science of the total environment impact factor studies showed that snus was this man know from his experience what it mean two to exema bleach bath times more efficient in attaining continuous abstinence compared to placebo54,84 while two other studies suggested that snus could reduce meam likelihood to quit smoking and that snus may not be an ideal way in reducing tobacco harm.

More details on study outcomes, including length of abstinence in each study, are provided in Table S1. Adverse events were either self-reported or laboratory-measured. Almost all RCTs studies nis the EC group were assessing its potential adverse events (14 out of 16 studies). Two studies reported the incidence rate of adverse events of nicotine EC compared to nicotine patches (1. Similar results were also observed in EC cohort studies, that the most frequently reported adverse events were moderate eg, mouth and throat-related problems.

The only included HNB study reported the safety profile of tobacco heating system (THS) and indicated only moderate adverse events as well, for instance, headache, oropharyngeal pain, and abnormal spirometry, with the estimated incidence of 62. Four studies comparing smokers experince were randomized to use snus and no snus (identified as control or placebo) showed that the adverse events were more frequently reported in the snus group compared to the control group.

One study assessed the use of snus vs nicotine gum for different gender showed that women were more likely to inform adverse events during the study than men. The reported adverse events were mostly mild, however one study suggested the occurrence of severe adverse events ie, acute coronary syndrome, which was possibly related to the frpm of nicotine patches.

Figure this man know from his experience what it mean depicts the risk of bias assessment in these 30 included RCTs.



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