ObjectiveTo review and summarise the current evidence on the uptake of combustible cigarette smoking following e-cigarette use in non-smokers—including never-smokers, people not currently smoking and past smokers—through an umbrella review, systematic review and meta-analysis.DesignUmbrella review, systematic review and meta-analysis.Data sourcesPubMed, Scopus, Web of Science, PsychINFO (Ovid), Medline (Ovid) and Wiley Cochrane Library up to April 2020.ResultsOf 6225 results, 25 studies of non-smokers—never, not current and former smokers—with a baseline measure of e-cigarette use and an outcome measure of combustible smoking uptake were included. All 25 studies found increased risk of smoking uptake with e-cigarette exposure, although magnitude varied substantially. Using a random-effects model, comparing e-cigarette users versus non-e-cigarette users, among never-smokers at baseline the OR for smoking initiation was 3.25 (95% CI 2.61 to 4.05, I2 85.7%) and among non-smokers at baseline the OR for current smoking was 2.87 (95% CI 1.97 to 4.19, I2 90.1%). Among former smokers, smoking relapse was higher in e-cigarette users versus non-users (OR=2.40, 95% CI 1.50 to 3.83, I2 12.3%).ConclusionsAcross multiple settings, non-smokers who use e-cigarettes are consistently more likely than those avoiding e-cigarettes to initiate combustible cigarette smoking and become current smokers. The magnitude of this risk varied, with an average of around three times the odds. Former smokers using e-cigarettes have over twice the odds of relapse as non-e-cigarettes users. This study is the first to our knowledge to review and pool data on the latter topic.PROSPERO registration numberCRD42020168596.

Objective: To systematically review and meta-analyse evidence regarding the efficacy of electronic nicotine delivery systems (ENDS) as smoking cessation aids. Data Sources: PubMed, Scopus, Web of Science, PsycINFO, MEDLINE and Cochrane Library were searched up to February-March 2020 (PROSPERO registration CRD42020170692). Study selection: Published peer-reviewed randomised controlled trials (RCTs) of the efficacy of ENDS for sustained cessation of combustible tobacco smoking and/or nicotine use, compared with no intervention, placebo or nicotine replacement therapy (NRT) by intention-to-treat, with a minimum of four months follow-up. Data Extraction: Data were extracted independently into a pre-specified template. Risk of bias was assessed with the Cochrane Collaboration′s tool and evidence quality rated using GRADE. Data Synthesis: From 3,973 titles identified, nine RCTs were identified; 330 of 5,445 smokers randomised quit. Smoking cessation did not differ significantly for randomisation to ENDS versus: no intervention (three studies, random-effects meta-analysis RR 1.95; 95%CI 0.90-4.22); placebo (three studies, 1.61; 0.93-2.78) or NRT (three studies; 1.25; 0.74-2.11). Fixed-effects sensitivity analyses showed significant results for ENDS vs NRT (1.43; 1.10-1.86). Smokers randomised to ENDS were substantially more likely than control to use nicotine at follow-up. Overall evidence quality was low. Considering only studies without potential competing interests further limited evidence but did not materially change conclusions. Conclusions: There is insufficient evidence that ENDS are efficacious for smoking cessation compared to no intervention, placebo or NRT. Results are promising, particularly for therapeutic use, but vary according to analytic method. ENDS may lead to greater ongoing nicotine exposure than other smoking cessation methods.

Introduction: Several systemic therapies have demonstrated a survival advantage in metastatic castration resistant prostate cancer (mCRPC). Access to these medications varies significantly worldwide. In Australia until recently, patients must have received docetaxel first, unless unsuitable for chemotherapy, despite no evidence suggesting superiority over androgen receptor signalling inhibitors (ARSIs). Our study investigated real-world systemic treatment patterns in Australian patients with mCRPC. Methods:The electronic CRPC Australian Database (ePAD) was interrogated to identify mCRPC patients. Clinicopathological features, treatment and outcome data, stratified by first-line systemic therapies, were extracted. Comparisons between groups utilised Kruskal-Wallis tests and Chi-Square analyses. Time-to-event data were calculated using Kaplan-Meier methods and groups compared using log-rank tests. Factors influencing overall survival (OS) and time to treatment failure (TTF) were analysed through Cox proportional hazards regression models.Results: We identified 578 patients who received first-line systemic therapy for mCRPC. Enzalutamide (ENZ) was most commonly prescribed (n = 240, 41%), followed by docetaxel (DOC, n = 164, 28%) and abiraterone (AA, n = 100, 17%).Patients receiving ENZ or AA were older (79, 78.5 years respectively) compared with DOC (71 years, p = 0.001) and less likely to have ECOG performance status 0 (45%, 44%, 59% in ENZ, AA and DOC groups respectively p < 0.0001). Median TTF was significantly higher in those receiving ENZ (12.4 months) and AA (11.9 months) compared to DOC (8.3 months, p < 0.001). PSA50 response rates and OS were not statistically different. Time to developing CRPC > 12 months was independently associated with longer TTF (HR 0.67, p < 0.001) and OS (HR 0.49, p = 0.002). Conclusion:In our real-world population, ENZ and AA were common first-line systemic therapy choices, particularly among older patients and those with poorer

ObjectivesTo investigate the recent real‐world use of first‐generation antiandrogens (FGAs) in metastatic castration‐resistant prostate cancer (mCRPC) using a retrospective multicentre cohort study.Patients and MethodsThe electronic CRPC Australian Database (ePAD) was interrogated to identify patients with mCRPC. Clinicopathological features, treatment and outcome data, stratified by FGA use, were retrieved and reported through descriptive statistics. Survival analyses were calculated using the Kaplan–Meier method and groups compared using log‐rank tests. Factors influencing overall survival (OS) were analysed using Cox proportional hazards regression model.ResultsWe identified 634 patients with mCRPC, enrolled in ePAD between January 2016 and March 2019, including 322 (51%) who received FGAs. The median follow‐up was 21.9 months. Patients treated with FGAs were more likely to have lower International Society of Urological Pathologists (ISUP) grade group (P = 0.04), longer median time to CRPC (25.6 vs 16.0 months, P < 0.001), and were less likely to have visceral metastases (5.0% vs 11.2%, P = 0.005) or to have received upfront docetaxel (P < 0.001). A ≥50% reduction from pre‐treatment prostate‐specific antigen (PSA) level (PSA50 response) during FGA treatment occurred in 119 (37%) patients and was independently associated with improved OS (hazard ratio 0.233, P < 0.001). Prior FGA treatment did not significantly influence the selection of subsequent life‐prolonging treatments for mCRPC or their PSA50 response rates.ConclusionIn our present cohort, FGAs were commonly used in lower‐risk mCRPC and their use did not significantly influence the choice or duration of subsequent systemic therapy. A PSA50 response to FGA therapy was an independent favourable prognostic marker associated with improved OS.

Introduction: Combustible tobacco smoking is a leading cause of death and disability worldwide. E-cigarettes are promoted for smoking cessation, but evidence on how their use relates to smoking uptake is limited. Methods: We searched PubMed, Scopus, Web of Science, PsychINFO (Ovid), Medline (Ovid) and Wiley Cochrane Library in April 2020. Studies of non-smokers - never, not current, and former smokers - with a baseline measure of e-cigarette use and an outcome measure of combustible smoking uptake were included. Results: Of 6,225 studies identified, 3 systematic reviews (incorporating 13 primary research studies) and 12 additional studies were included in umbrella and top-up systematic reviews, respectively. All 25 studies found increased risk of smoking uptake with e-cigarette exposure, although magnitude varied substantially. Using a random-effects model, comparing e-cigarette users versus non-e-cigarette users, among never-smokers at baseline the odds ratio (OR) for smoking initiation was 3.25 (95%CI 2.61-4.05, I2 85.7%) and among non-smokers at baseline the OR for current smoking was 2.87 (95%CI 1.97-4.19, I2 90.1%). Among former smokers, smoking relapse was higher in e-cigarette users versus non-users (OR=2.40, 95% CI 1.50-3.83, I2 12.3%). Conclusions: Across multiple settings, non-smokers who use e-cigarettes are consistently more likely than non-e-cigarettes users to initiate combustible cigarette smoking and become current smokers; risk magnitude varied, with an average of around three times the odds. Former smokers using e-cigarettes have over twice the odds of relapse as non-e-cigarettes users. This study is the first to our knowledge to review and pool data on the latter topic.