A Systematic Review Investigating Associations Between E-Cigarette Use Among Former Cigarette Smokers and Relapse to Smoking Cigarettes.

As e-cigarette use has steadily increased over the recent years, the public health interest in the potential implications of e-cigarette use on cigarette smoking has grown in parallel. With strict adherence to PRISMA guidelines, this systematic review examined the potential associations between e-cigarette use and relapse to cigarette smoking among former cigarette smokers. The protocol was registered on November 06, 2018 (PROSPERO 2018 CRD42018115674). Literature searches were executed from January 01, 2007 to August 20, 2022 and search results were screened according to the PICOS review method. One RCT and 10 adjusted studies examined relapse to cigarette smoking (evidence grade "moderate") among regular e-cigarette users, reporting mixed and inconsistent findings according to varying definitions of e-cigarette use and relapse. Findings were similarly inconsistent among the 8 adjusted studies examining relapse to cigarette smoking among non-regular e-cigarette users. The inconsistency in findings among studies evaluating regular measures of e-cigarette use, combined with the numerous methodological flaws in the overall body of literature, limit the generalizability of results associated with a causal association between e-cigarette use and relapse to cigarette smoking. Based on findings from this review, more robust studies are required to determine whether a causal association exists between e-cigarette use and relapse to cigarette smoking. Future studies should apply consistent measures of regular e-cigarette use to examine causality with future use patterns, and sufficiently account for known or suspected confounding variables to support inform determinations related to e-cigarette use and cigarette smoking behaviors.

Study title: A systematic review of RCTs to examine the risk of adverse cardiovascular events with nicotine use.

Associations between cigarette smoking and increased risk of cardiovascular disease are well established. However, it is unclear whether the association is mediated by exposure to nicotine and/or to other constituents in cigarette smoke. The objective of this systematic review and meta-analysis of randomized control trials (RCTs) was to identify any potential associations between exposure to nicotine and the risk of clinically diagnosed adverse cardiovascular events in adult current users and nonusers of tobacco products. Among 1,996 results, 42 studies, comparing nicotine and non-nicotine groups, were included and were both qualitatively and quantitatively synthesized across the outcomes of arrhythmia, nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death. The majority of studies evaluating nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death reported no events that occurred in either the nicotine or non-nicotine control groups. Among the studies that reported events, rates of adverse events were similarly low between both groups. Consistent with findings from previous systematic reviews and meta-analyses, pooled data showed that rates for arrhythmia, nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death were not significantly different between nicotine and non-nicotine groups. The overall quality of the body of evidence for each of the four outcomes of interest was graded as "moderate," limited only by the imprecision of results. The findings of this systematic review and meta-analysis indicate that, with moderate certainty, there are no significant associations between the use of nicotine and the risk of clinically diagnosed adverse cardiovascular events-specifically, arrhythmia, nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death.

A systematic review of preclinical studies evaluating the association between nicotine and the initiation and progression of cancer.

Background: The association between cigarette smoking and the increased risk of many cancers is well established. Conversely, epidemiological studies of smokeless tobacco demonstrate decreased risk, or no elevated risk, of certain cancers versus smoking. However, it is unclear what role, if any, nicotine plays in these associations. The objective of this systematic review was to synthesize the available evidence from preclinical studies that examined the potential association between nicotine and the initiation and/or progression of cancer. Methods: MEDLINE, Embase, PsychInfo, and Cochrane Database of Systematic Reviews were searched for articles published from inception until February 13, 2022. Studies were eligible for inclusion if they evaluated animal cancer or tumor models, compared nicotine and non-nicotine groups, and evaluated measures of cancer initiation or progression. Results: Among 1,137 identified articles, 61 were included in qualitative synthesis. Twelve studies reported data on tumor initiation, and 54 studies reported data on tumor progression. The majority of the tumor initiation studies did not identify an association between nicotine exposure and an increased risk of spontaneous tumor initiation. Results of tumor progression studies were inconsistent and varied across the reported measures, cancer type being evaluated, and animal cancer model used. Overall, the quality of reporting was poor, with many studies not demonstrating a high level of internal and/or external validity. Conclusions: In conclusion, although animal models have provided invaluable data for human health risk assessments of chemical exposures, the heterogeneity across the studies included in this systematic review make the interpretation and generalizability of the results difficult.

A Systematic Review and Meta-analysis of the Association between E-cigarette Use among Cigarette Smokers and Quit Attempts Made to Abstain from Cigarette Smoking.

Objective: Following AMSTAR 2 and PRISMA guidelines, in this synthesis of evidence we sought to identify and characterize any associations between e-cigarette use among cigarette smokers and cigarette smoking quit attempts. Methods: We queried 3 databases from January 1, 2007 to January 5, 2021. Search results were screened using the PICOS review method. Included studies examined e-cigarette use and cigarette smoking quit attempts across e-cigarette use statuses. Risk of bias was assessed according to the Agency for Healthcare Research and Quality Evidence-Based Practice Center approach. Finally, 4 random-effects models compared e-cigarette users and non- e-cigarette-users in terms of past year and prospective (6 to 12 months) cigarette smoking quit attempts. Results: We qualitatively synthesized 17 adjusted studies for this review. Two meta-analyses showed past year quit attempts were significantly associated with current e-cigarette users and 2 prospective data analyses found no significant association. Conclusions: The results of the meta- analyses emphasize temporality in the association between e-cigarette use and cigarette smoking quit attempts. Numerous methodological limitations, including inadequate definitions of e-cigarette use and non-adjustment for confounding variables, limit the confidence in conclusions that can be drawn on the causal association between e-cigarette use and cigarettes smoking quit attempts.

Reporting and methodological quality of systematic literature reviews evaluating the associations between e-cigarette use and cigarette smoking behaviors: a systematic quality review.

INTRODUCTION: Several published systematic reviews have examined the potential associations between e-cigarette use and cigarette smoking, but their methodological and/or reporting quality have not yet been assessed. This systematic quality review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and AMSTAR (A MeaSurement Tool to Assess systematic Reviews) 2 to evaluate the quality of systematic reviews investigating potential associations between e-cigarette use and cigarette smoking. MATERIALS AND METHODS: PubMed/MEDLINE, Embase, and PsycINFO were searched from 01 January 2007 to 24 June 2020. Methodological quality was assessed using AMSTAR 2, and reporting quality was assessed using PRISMA guidelines. RESULTS: Of 331 potentially relevant systematic reviews, 20 met predefined inclusion criteria. Most reviews (n = 15; 75%) reported on e-cigarette use and cigarette smoking cessation, while three reported on e-cigarette use and cigarette smoking initiation (15%); and two reported on cigarette smoking initiation and cessation (10%). According to AMSTAR 2 guidelines, 18 of the 20 reviews (90%) were "critically low" in overall confidence of the results, while two were ranked "low." Additionally, reporting quality varied across the reviews, with only 60% reporting at least half of the PRISMA items. DISCUSSION: Methodological limitations were identified across reviews examining potential associations between e-cigarette use and cigarette smoking behaviors, indicating that findings from these reviews should be interpreted with caution. CONCLUSIONS: Future systematic reviews in this field should strive to adhere to AMSTAR 2 and PRISMA guidelines, to provide high quality syntheses of the available data with transparent and complete reporting.

Treatment with C1-esterase inhibitor concentrate in type I or II hereditary angioedema: a systematic literature review.

Hereditary angioedema (HAE) due to C1 esterase inhibitor (HAE-C1-INH) deficiency is a rare genetic disorder presenting with recurrent episodes of skin swellings, abdominal pain attacks, and potentially fatal laryngeal edema. This study was designed to review the efficacy and safety of pasteurized, human, plasma-derived C1-INH concentrate for the treatment of patients with HAE-C1-INH. A systematic search of electronic databases up to December 2011 was performed without language or date restrictions. Two reviewers completed the study selection using predefined inclusion criteria, tabulated, and analyzed the data. The data were inappropriate for meta-analysis; thus, a qualitative synthesis was performed. We identified 89 studies (≍2000 patients) that investigated C1-INH. Replacement therapy with C1-INH significantly shortened time to onset of symptom relief in HAE attacks compared with placebo in a randomized controlled trial, and similar improvements were consistently reported in observational and descriptive studies, accompanied by improvements in patients' quality of life. C1-INH has been shown to be effective for patients receiving home therapy and short- and long-term prophylaxis. Treatment with C1-INH was generally well tolerated. Administration of C1-INH was not associated with transmission of viruses or development of autoantibodies irrespective of treatment duration. This research provides additional confirmation of the efficacy of C1-INH in the treatment and prevention of HAE attacks. C1-INH is generally safe and well tolerated and has an excellent safety record for over 25 years of clinical use.

Prostaglandin analogues for ophthalmic use: a cost-effectiveness analysis.

BACKGROUND: The objective of this study was to perform an economic analysis of the cost-effectiveness of prostaglandin analogues for the treatment of increased intraocular pressure (IOP). Prostaglandin analogues for ophthalmic use are more costly than alternative agents for the lowering of IOP. An important policy decision is whether to support continued open listing of these agents or to restrict them to limited use status. METHODS: The cost-effectiveness of prostaglandin analogues was assessed using a decision analytic model. Latanoprost was compared with timolol, dorzolamide, and brimonidine, and travoprost was compared with timolol separately. The effectiveness data used for this economic analysis were the number of millilitres of mercury of IOP reduction compared with baseline and the incidence of adverse events resulting in a withdrawal of the patient from the study. Sensitivity analyses were conducted to assess the robustness of the study results. RESULTS: Compared with latanoprost, dorzolamide was not a cost-effective strategy. Compared with brimonidine, latanoprost provided a higher IOP reduction with an incremental cost-effectiveness ratio of $16.17 (base case), but the additional IOP reduction with latanoprost was obtained at a cost higher than the average cost per millimetre of mercury reduction obtained with brimonidine. Compared with timolol, latanoprost and travoprost had a positive incremental cost-effectiveness ratio of $34.48 and $39.06, respectively. INTERPRETATION: For the first-line treatment of glaucoma and elevated IOP, latanoprost is a more cost-effective strategy than dorzolamide and brimonidine. Latanoprost and travoprost are more effective than timolol but also more expensive. For those for whom timolol is not contraindicated, it would be preferable, from a cost-effectiveness standpoint, to initiate treatment with timolol and reserve the prostaglandin analogues as an alternative treatment or as add-on therapy for patients not achieving a clinical response with timolol. Better treatment compliance associated with these analogues improves their cost-effectiveness.

Embryogenesis in the Presence of Blockers of Mechanosensitive Ion Channels: (embryogenesis/mechanosensitive ion channels/channel blockers/Xenopus/ascidians).

Certain developmental events are thought to be controlled by mechanical tension, but the nature of the transduction mechanism for sensing and responding to tension changes is unknown. A good candidate for such a sensing system would be stretch-activated (SA) ion channels, a type of mechanosensitive (MS) ion channel found in many preparations including the oocytes or embryos of ascidians, fish, and amphibians. To test the hypothesis that SA channel activation is important for early embryogenesis, we treated amphibian and ascidian eggs and embryos with inhibitors of MS ion channels. Xenopus laevis eggs and embryos were treated with gadolinium (Gd3+ ) concentrations up to 100 times the Kd for SA channel inhibition. Boltenia villosa eggs and embryos were exposed to three agents (Gd3+ , tubocurarine, and gallamine) which are known to block SA channels in other organisms. None of these drugs interfered with morphogenesis in a manner that would suggest SA channel activity is critical to early embryogenesis.