Efficacy of interventions targeted at physician prescribers of opioids for chronic non-cancer pain: an overview of systematic reviews.

BACKGROUND: To combat the opioid crisis, interventions targeting the opioid prescribing behaviour of physicians involved in the management of patients with chronic non-cancer pain (CNCP) have been introduced in clinical settings. An integrative synthesis of systematic review evidence is required to better understand the effects of these interventions. Our objective was to synthesize the systematic review evidence on the effect of interventions targeting the behaviours of physician opioid prescribers for CNCP among adults on patient and population health and prescriber behaviour. METHODS: We searched MEDLINE, Embase, and PsycInfo via Ovid; the Cochrane Database of Systematic Reviews; and Epistemonikos. We included systematic reviews that evaluate any type of intervention aimed at impacting opioid prescriber behaviour for adult CNCP in an outpatient setting. RESULTS: We identified three full texts for our review that contained 68 unique primary studies. The main interventions we evaluated were structured prescriber education (one review) and prescription drug monitoring programmes (PDMPs) (two reviews). Due to the paucity of data available, we could not determine with certainty that education interventions improved outcomes in deprescribing. There is some evidence that PDMPs decrease the number of adverse opioid-related events, increase communication among healthcare workers and patients, modify healthcare practitioners' approach towards their opioid prescribed patients, and offer more chances for education and counselling. CONCLUSIONS: Our overview explores the possibility of PDMPs as an opioid deprescribing intervention and highlights the need for more high-quality primary research on this topic.

Interventions for Preventing E-Cigarette Use Among Children and Youth: A Systematic Review.

INTRODUCTION: Many nonregulatory interventions targeting children and youth have been implemented at three levels: directed at the individual (e.g., interactive video games), delivered to students at school (e.g., campus bans), and launched in the community (e.g., mass media campaigns). This systematic review aims to synthesize the evidence on the effectiveness of interventions aimed at preventing e-cigarette initiation among children and youth. METHODS: MEDLINE, CINAHL, Embase, APA PsycINFO, and Web of Science Core Collection were searched for papers published between January 1, 2004 and September 1, 2022 that reported more than one outcome on vaping prevention among individuals aged less than 21-years-old: vaping prevalence/incidence, initiation intentions, knowledge/attitudes, and other tobacco product use prevalence/initiation intentions. Interventions were at the individual, school, or community level. The risk of bias was assessed using ROBINS-I and RoB 1. RESULTS: Thirty-nine publications met the eligibility criteria. Fourteen individually-based (4 parental monitoring, 3 video games, 2 text messages, 3 graphic message themes, 2 healthcare), 19 school-based (14 educational and skill interventions, 5 vape-free policies/bans), and 6 community-based (3 social media, 3 mass media campaigns) interventions were reported. E-cigarette initiation prevention was observed with high perceived parental monitoring; however, the cross-sectional study designs precluded causal claims. There was promising but limited evidence that social-emotional skills curricula and peer leader programming prevented vaping initiation. DISCUSSION: Some individual- and school-based interventions showed promise for preventing e-cigarette initiation among children and youth.

Regulatory Strategies for Preventing and Reducing Nicotine Vaping Among Youth: A Systematic Review.

INTRODUCTION: Many jurisdictions have implemented different regulatory strategies to reduce vaping among youth. The objective of this systematic review is to synthesize the evidence of the effectiveness of different regulatory strategies for preventing and reducing nicotine vaping among youth. METHODS: Five electronic databases were searched from January 1, 2004 to July 17, 2022 for primary studies examining state/provincial or national regulations targeting vaping among youth (aged 12-21 years) in high-income countries. The primary outcome was vaping prevalence. Included studies were qualitatively synthesized through systematic review. RESULTS: The systematic review included 30 studies. There was insufficient evidence to recommend age restrictions (n=16), restrictions on location of use (n=1), and mixed/combined regulations (n=3). Flavor bans (n=4), sales licenses (n=2), and taxation (n=2) were generally shown to be associated with decreased rates of youth vaping. Warning labels (n=2) were associated with a decreased desire to initiate vaping. Included studies had moderate-to-serious risks of bias. DISCUSSION: Although several regulatory interventions have been shown to be effective at reducing vaping among youth, evidence is insufficient to recommend a specific type of regulation. Regulatory authorities could implement various regulations targeting the price, accessibility, and desirability (i.e., flavors and packaging) of E-cigarettes.

Roadside screening tests for cannabis use: A systematic review.

As more countries legalize recreational cannabis, roadside screening programs are imperative to detect and deter driving under the influence of cannabis. This systematic review evaluated roadside screening tests for cannabis use. We searched six databases (inception-March 2020) and grey literature sources for primary studies evaluating test characteristics of roadside screening tests for cannabis use compared to laboratory tests for cannabinoids in blood or oral fluid. The synthesis was focused on sensitivity and specificity of delta-9-tetrahydrocannabinol (THC) detection. 101 studies were included. Oral fluid tests were higher in specificity and lower in sensitivity compared to urine tests when evaluated against blood laboratory tests. Oral fluid tests were higher in sensitivity and similar in specificity compared to observational tests when evaluated against blood and oral fluid laboratory tests. Sensitivity was variable among oral fluid tests; two instrumented immunoassays (Draeger DrugTest 5000 [5 ng/mL THC cut-off] and Alere DDS 2 Mobile Test System) appeared to perform best, but definitive conclusions could not be drawn due to imprecise estimates. Specificities were similar. Overall, oral fluid tests showed the most promise for use in roadside screening for blood THC levels over legal limits; their continued development and testing are warranted. Urine tests are generally inadvisable, and observational tests require sensitivity improvements.

The Impact of Cannabis Decriminalization and Legalization on Road Safety Outcomes: A Systematic Review.

INTRODUCTION: There is substantial debate concerning the impact of cannabis decriminalization and legalization on road safety outcomes. METHODS: Seven databases were systematically searched: Embase, MEDLINE, and PsycINFO through Ovid as well as Web of Science Core Collection, SafetyLit, Criminal Justice Database (ProQuest), and Transport Research International Documentation (from inception to June 16, 2021). Eligible primary studies examined group-level cannabis decriminalization or legalization and a road safety outcome in any population. RESULTS: A total of 65 reports of 64 observational studies were eligible, including 39 that applied a quasi-experimental design. Studies examined recreational cannabis legalization (n=50), medical cannabis legalization (n=22), and cannabis decriminalization (n=5). All studies except 1 used data from the U.S. or Canada. Studies found mixed impacts of legalization on attitudes, beliefs, and self-reported driving under the influence. Medical legalization, recreational legalization, and decriminalization were associated with increases in positive cannabis tests among drivers. Few studies examined impacts on alcohol or other drug use, although findings suggested a decrease in positive alcohol tests among drivers associated with medical legalization. Medical legalization was associated with reductions in fatal motor-vehicle collisions, whereas recreational legalization was conversely associated with increases in fatal collisions. DISCUSSION: Increased cannabis positivity may reflect changes in cannabis use; however, it does not in itself indicate increased impaired driving. Subgroups impacted by medical and recreational legalization, respectively, likely explain opposing findings for fatal collisions. More research is needed concerning cannabis decriminalization; the impacts of decriminalization and legalization on nonfatal injuries, alcohol and other drugs; and the mechanisms by which legalization impacts road safety outcomes.

Interventions for physician prescribers of opioids for chronic non-cancer pain: protocol for an overview of systematic reviews.

INTRODUCTION: Interventions targeting behaviours of physician prescribers of opioids for chronic non-cancer pain have been introduced to combat the opioid crisis. Systematic reviews have evaluated effects of specific interventions (eg, prescriber education, prescription drug monitoring programmes) on patient and population health outcomes and prescriber behaviour. Integration of findings across intervention types is needed to better understand the effects of prescriber-targeted interventions. METHODS AND ANALYSIS: We will conduct an overview of systematic reviews. Eligible systematic reviews will include primary studies that evaluated any intervention targeting the behaviours of physician prescribers of opioids for chronic non-cancer pain in an outpatient or mixed setting, compared with no intervention, usual practice or another active or control intervention. Eligible outcomes will pertain to the intervention effect on patient and population health or opioid prescribing behaviour. We will search MEDLINE, Embase and PsycInfo via Ovid; the Cochrane Database of Systematic Reviews and Epistemonikos from inception. We will also hand search reference lists for additional publications. Screening and data extraction will be conducted independently by two reviewers, with disagreements resolved by consensus or consultation with a third reviewer. The risk of bias of included systematic reviews will be assessed in duplicate by two reviewers using the Risk of Bias in Systematic Reviews tool. Results will be synthesised narratively by intervention type and grouped by outcome. To assist with result interpretation, outcomes will be labelled as intended or unintended according to intervention objectives, and as positive, negative, evidence of no effect or inconclusive evidence according to effect on the population (for patient and population health outcomes) or intervention objectives (for prescriber outcomes). ETHICS AND DISSEMINATION: As the proposed study will use published data, ethics approval is not required. Dissemination of results will be achieved through publication of a manuscript in a peer-reviewed journal and conference presentations. PROSPERO REGISTRATION NUMBER: CRD42020156815.

Effectiveness of Interventions for Prevention of Common Infections Among Opioid Users: A Systematic Review of Systematic Reviews.

Background: The North American opioid crisis is marked by high opioid-related mortality and morbidity, including opioid use-associated infections (OUAIs). Users of pharmaceutical and non-pharmaceutical opioids are at an increased risk of acquiring hepatitis C (HCV), human immunodeficiency virus (HIV), and other infections. No high-level evidence, however, has been synthesized regarding effectiveness of interventions to prevent OUAIs in legal, and illegal/mixed opioid users. The aim of the study is to synthesize available systematic review (SR)-level evidence on the scope and effectiveness of interventions to prevent OUAIs among opioid users. Methods: A SR of SRs approach was applied. We searched PubMed, Embase, PsycINFO, Cochrane Database of Systematic Reviews, Epistemonikos and Google Scholar from inception to September 2020. Data selection and extraction were performed independently by three researchers. Risk of bias and quality of evidence were assessed using the AMSTAR2 tool. Results were narratively synthesized. Strength of evidence for each category was reported. Results: Eleven of twelve identified SRs included interventions to prevent HCV/HIV transmission in persons who inject drugs (PWID), including opioids. One SR evaluated interventions to prevent recurrent infectious endocarditis. There was sufficient and tentative SR of SRs-level evidence for the effectiveness of opioid substitution therapy (OST) in preventing HIV and HCV, respectively. We found tentative evidence to support effectiveness of needle/syringe exchange programs (NSP) in HIV prevention, and sufficient evidence to support effectiveness of the combined OST and NSP in HCV prevention. There was insufficient SR-level evidence to support or discount effectiveness of other interventions to prevent OUAIs. No SR focused on non-PWID populations. Conclusion: SR-level evidence supports the use of OST, NSP, and combined interventions for the reduction of HCV and HIV transmission in PWID. More research on prevention of other OUAIs and on prevention of OUAIs in non-PWID populations is urgently needed. Systematic Review Registration: Registered in PROSPERO on July 30, 2020. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=195929, identifier: #195929.

The Effect of Overdose Education and Naloxone Distribution: An Umbrella Review of Systematic Reviews.

Background. Opioids contribute to more than 60 000 deaths annually in North America. While the expansion of overdose education and naloxone distribution (OEND) programs has been recommended in response to the opioid crisis, their effectiveness remains unclear. Objectives. To conduct an umbrella review of systematic reviews to provide a broad-based conceptual scheme of the effect and feasibility of OEND and to identify areas for possible optimization. Search Methods. We conducted the umbrella review of systematic reviews by searching PubMed, Embase, PsycINFO, Epistemonikos, the Cochrane Database of Systematic Reviews, and the reference lists of relevant articles. Briefly, an academic librarian used a 2-concept search, which included opioid subject headings and relevant keywords with a modified PubMed systematic review filter. Selection Criteria. Eligible systematic reviews described comprehensive search strategies and inclusion and exclusion criteria, evaluated the quality or risk of bias of included studies, were published in English or French, and reported data relevant to either the safety or effectiveness of OEND programs, or optimal strategies for the management of opioid overdose with naloxone in out-of-hospital settings. Data Collection and Analysis. Two reviewers independently extracted study characteristics and the quality of included reviews was assessed in duplicate with AMSTAR-2, a critical appraisal tool for systematic reviews. Review quality was rated critically low, low, moderate, or high based on 7 domains: protocol registration, literature search adequacy, exclusion criteria, risk of bias assessment, meta-analytical methods, result interpretation, and presence of publication bias. Summary tables were constructed, and confidence ratings were provided for each outcome by using a previously modified version of the Royal College of General Practitioners' clinical guidelines. Main Results. Six systematic reviews containing 87 unique studies were included. We found that OEND programs produce long-term knowledge improvement regarding opioid overdose, improve participants' attitudes toward naloxone, provide sufficient training for participants to safely and effectively manage overdoses, and effectively reduce opioid-related mortality. High-concentration intranasal naloxone (> 2 mg/mL) was as effective as intramuscular naloxone at the same dose, whereas lower-concentration intranasal naloxone was less effective. Evidence was limited for other naloxone formulations, as well as the need for hospital transport after overdose reversal. The preponderance of evidence pertained persons who use heroin. Author's Conclusions. Evidence suggests that OEND programs are effective for reducing opioid-related mortality; however, additional high-quality research is required to optimize program delivery. Public Health Implications. Community-based OEND programs should be implemented widely in high-risk populations.

The Effect of Overdose Education and Naloxone Distribution: An Umbrella Review of Systematic Reviews.

Background. Opioids contribute to more than 60 000 deaths annually in North America. While the expansion of overdose education and naloxone distribution (OEND) programs has been recommended in response to the opioid crisis, their effectiveness remains unclear. Objectives. To conduct an umbrella review of systematic reviews to provide a broad-based conceptual scheme of the effect and feasibility of OEND and to identify areas for possible optimization. Search Methods. We conducted the umbrella review of systematic reviews by searching PubMed, Embase, PsycINFO, Epistemonikos, the Cochrane Database of Systematic Reviews, and the reference lists of relevant articles. Briefly, an academic librarian used a 2-concept search, which included opioid subject headings and relevant keywords with a modified PubMed systematic review filter. Selection Criteria. Eligible systematic reviews described comprehensive search strategies and inclusion and exclusion criteria, evaluated the quality or risk of bias of included studies, were published in English or French, and reported data relevant to either the safety or effectiveness of OEND programs, or optimal strategies for the management of opioid overdose with naloxone in out-of-hospital settings. Data Collection and Analysis. Two reviewers independently extracted study characteristics and the quality of included reviews was assessed in duplicate with AMSTAR-2, a critical appraisal tool for systematic reviews. Review quality was rated critically low, low, moderate, or high based on 7 domains: protocol registration, literature search adequacy, exclusion criteria, risk of bias assessment, meta-analytical methods, result interpretation, and presence of publication bias. Summary tables were constructed, and confidence ratings were provided for each outcome by using a previously modified version of the Royal College of General Practitioners' clinical guidelines. Main Results. Six systematic reviews containing 87 unique studies were included. We found that OEND programs produce long-term knowledge improvement regarding opioid overdose, improve participants' attitudes toward naloxone, provide sufficient training for participants to safely and effectively manage overdoses, and effectively reduce opioid-related mortality. High-concentration intranasal naloxone (> 2 mg/mL) was as effective as intramuscular naloxone at the same dose, whereas lower-concentration intranasal naloxone was less effective. Evidence was limited for other naloxone formulations, as well as the need for hospital transport after overdose reversal. The preponderance of evidence pertained persons who use heroin. Author's Conclusions. Evidence suggests that OEND programs are effective for reducing opioid-related mortality; however, additional high-quality research is required to optimize program delivery. Public Health Implications. Community-based OEND programs should be implemented widely in high-risk populations.

Interventions to Prevent Drugged Driving: A Systematic Review.

CONTEXT: Literature suggests that cannabis legalization may increase fatal motor vehicle collisions. However, evidence on the effectiveness of interventions to prevent drugged driving is limited. EVIDENCE ACQUISITION: MEDLINE, PsycINFO, Web of Science, Embase, SafetyLit, Criminal Justice Database, Transport Research International Documentation, bibliographies, and relevant gray literature were searched systematically through May 2020. Randomized and nonrandomized studies of preventive interventions measuring drugged driving outcomes were included. Evidence certainty was judged per Grading of Recommendations Assessment, Development, and Evaluation guidelines to designate quality ratings from very low to high. EVIDENCE SYNTHESIS: The search identified 11 RCTs and 17 nonrandomized studies conducted predominantly among youth (aged 15-25 years; n=33,711 of 37,117 active research participants). In the public, cannabis packaging with health warnings increases the knowledge about drugged driving effects (high certainty); roadside drug testing can reduce drugged driving among cannabis users (moderate certainty); media campaigns may increase deterrent attitudes and knowledge (low certainty); and state sanctions, including traffic offense criminalization, license withdrawal, and per se drugged driving laws, may have little or no effect on drug-related fatalities or injuries (very low-low certainty). For youth or previous offenders, motivational interviewing can prevent drugged driving and driver education programs can increase knowledge (moderate certainty), whereas drug abuse prevention, substance abuse treatment, and driver rehabilitation may prevent drugged driving (very low certainty). CONCLUSIONS: Overall, there is evidence to support the interventions that may improve drugged driving knowledge, attitudes, and behaviors. However, the impact of such interventions on measures of drugged driving-related morbidity and mortality is uncertain. Further research is urgently required to address these gaps in knowledge.

Association between legalization of recreational cannabis and fatal motor vehicle collisions in the United States: an ecologic study.

BACKGROUND: With the recent legalization of recreational cannabis in Canada, cannabis-impaired driving is an important public safety concern. Our aim was to examine the association between recreational cannabis legalization and fatal motor vehicle collisions using data from the United States, which present a timely natural experiment of cannabis legalization. METHODS: We conducted an ecologic study using the number of fatal motor vehicle collisions and the associated number of deaths for US jurisdictions with legalized recreational cannabis (2007-2018) retrieved from the US Fatality Analysis Reporting System. We examined jurisdiction-specific rates of fatal motor vehicle collisions and associated deaths before and after recreational cannabis legalization using Poisson regression and meta-analyzed estimates across jurisdictions using DerSimonian and Laird random-effects models. RESULTS: After adjustment for calendar year, legalization was associated with increases in rates of fatal motor vehicle collisions (incidence rate ratio [IRR] 1.15, 95% confidence interval [CI] 1.06-1.26) and associated deaths (IRR 1.16, 95% CI 1.06-1.27). Differences between the first 12 months after legalization relative to subsequent months were inconclusive for rates of fatal motor vehicle collisions (IRR 0.92, 95% CI 0.84-1.02) and associated deaths (IRR 0.92, 95% CI 0.84-1.01). INTERPRETATION: Recreational cannabis legalization in the US was associated with a relative increased risk of fatal motor vehicle collisions of 15% and a relative increase in associated deaths of 16%, with no conclusive difference between the first and subsequent years after legalization. These findings raise concern that there could be a similar increase in fatal motor vehicle collisions and associated deaths in Canada following recreational cannabis legalization.

Non-medical cannabis use among Indigenous Canadians: A systematic review of prevalence and associated factors.

BACKGROUND: Indigenous Canadians may be at an increased risk of non-medical cannabis use. The aim of this review was to synthesize the prevalence of non-medical cannabis use and its associated factors among Indigenous Canadians. METHODS: We systematically searched MEDLINE, EMBASE, Web of Science, and Scopus from inception to January 29th, 2020 for publications reporting the prevalence of non-medical cannabis use among Indigenous Canadians. We included studies published in English after January 1st, 2000. Included publications were hand-searched for potentially relevant peer-reviewed and gray literature publications. Results were synthesized descriptively. RESULTS: We identified 16 peer-reviewed and 7 gray literature publications which met our inclusion criteria. All data were collected prior to cannabis legalization in Canada (October 17th, 2018). The most recent estimates of prevalence of use in the past year were 27% among on-reserve First Nations adults, 50% among off-reserve First Nations adults, and 60% among Nunavik Inuit. In youth, they were 45% among all Indigenous youth grades 9-12, 27% among on-reserve First Nations youth aged 12-17, and 69% in Nunavik Inuit aged 16-22. Direct comparisons indicated a 1.2-15 times higher prevalence of use in Indigenous compared to non-Indigenous youth. Factors associated with cannabis use in adults included younger age and male sex. In youth, factors included older age, poorer mental and physical health, and a poorer relationship with school. CONCLUSION: Results suggest that Indigenous Canadians are at a higher risk for non-medical cannabis use than the general Canadian population. Further research is warranted to inform the development of targeted interventions.

Effect of e-Cigarettes Plus Counseling vs Counseling Alone on Smoking Cessation: A Randomized Clinical Trial.

Importance: Electronic cigarettes (e-cigarettes) for smoking cessation remain controversial. Objective: To evaluate e-cigarettes with individual counseling for smoking cessation. Design, Setting, and Participants: A randomized clinical trial enrolled adults motivated to quit smoking from November 2016 to September 2019 at 17 Canadian sites (801 individuals screened; 274 ineligible and 151 declined). Manufacturing delays resulted in early termination (376/486 participants, 77% of target). Outcomes through 24 weeks (March 2020) are reported. Interventions: Randomization to nicotine e-cigarettes (n = 128), nonnicotine e-cigarettes (n = 127), or no e-cigarettes (n = 121) for 12 weeks. All groups received individual counseling. Main Outcomes and Measures: The primary end point was point prevalence abstinence (7-day recall, biochemically validated using expired carbon monoxide) at 12 weeks, changed from 52 weeks following early termination. Participants missing data were assumed to be smoking. The 7 secondary end points, examined at multiple follow-ups, were point prevalence abstinence at other follow-ups, continuous abstinence, daily cigarette consumption change, serious adverse events, adverse events, dropouts due to adverse effects, and treatment adherence. Results: Among 376 randomized participants (mean age, 52 years; 178 women [47%]), 299 (80%) and 278 (74%) self-reported smoking status at 12 and 24 weeks, respectively. Point prevalence abstinence was significantly greater for nicotine e-cigarettes plus counseling vs counseling alone at 12 weeks (21.9% vs 9.1%; risk difference [RD], 12.8 [95% CI, 4.0 to 21.6]) but not 24 weeks (17.2% vs 9.9%; RD, 7.3 [95% CI, -1.2 to 15.7]). Point prevalence abstinence for nonnicotine e-cigarettes plus counseling was not significantly different from counseling alone at 12 weeks (17.3% vs 9.1%; RD, 8.2 [95% CI, -0.1 to 16.6]), but was significantly greater at 24 weeks (20.5% vs 9.9%; RD, 10.6 [95% CI, 1.8 to 19.4]). Adverse events were common (nicotine e-cigarette with counseling: 120 [94%]; nonnicotine e-cigarette with counseling: 118 [93%]; counseling only: 88 [73%]), with the most common being cough (64%) and dry mouth (53%). Conclusions and Relevance: Among adults motivated to quit smoking, nicotine e-cigarettes plus counseling vs counseling alone significantly increased point prevalence abstinence at 12 weeks. However, the difference was no longer significant at 24 weeks, and trial interpretation is limited by early termination and inconsistent findings for nicotine and nonnicotine e-cigarettes, suggesting further research is needed. Trial Registration: ClinicalTrials.gov Identifier: NCT02417467.

Meta-Analysis of Complete versus Culprit-Only Revascularization in Patients with ST-Segment Elevation Myocardial Infarction and Multivessel Coronary Disease.

Approximately half of patients with ST-segment elevation myocardial infarction (STEMI) present with noninfarct related multivessel coronary artery disease (CAD) during primary percutaneous coronary intervention (PCI). However, questions remain concerning whether patients with STEMI and multivessel CAD should routinely undergo complete revascularization. Our objective was to compare the risks of major cardiovascular outcomes and procedural complications in patients with STEMI and multivessel CAD randomized to complete revascularization versus culprit-only PCI. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing complete revascularization to culprit-only PCI. RCTs were identified via a systematic search of MEDLINE, Embase, and Cochrane CENTRAL. Count data were pooled using DerSimonian and Laird random-effects models with inverse variance weighting to obtain relative risks (RRs) and 95% confidence intervals (CIs). A total of 9 RCTs (n = 6,751) were included, with mean/median follow-up times ranging from 6 to 36 months. Compared with culprit-only PCI, complete revascularization was associated with a substantial reduction in major adverse cardiovascular events (13.1% vs 22.1%; RR: 0.54; 95%CI: 0.43 to 0.66), repeat myocardial infarction (4.9% vs 6.8%; RR: 0.64; 95%CI: 0.48 to 0.84), and repeat revascularization (3.7% vs 12.3%; RR: 0.33; 95%CI: 0.25 to 0.44). Complete revascularization may have beneficial effects on all-cause and cardiovascular mortality, but 95%CIs were wide. Findings for stroke, major bleeding, and contrast-induced acute kidney injury were inconclusive. In conclusion, complete coronary artery revascularization appears to confer benefit over culprit-only PCI in patients with STEMI and multivessel CAD, and should be considered a first-line strategy in these patients.

A Randomized Controlled Trial Evaluating the Efficacy of E-Cigarette Use for Smoking Cessation in the General Population: E3 Trial Design.

BACKGROUND: Smoking cessation improves morbidity and mortality among smokers who achieve long-term abstinence. Many smokers are using electronic cigarettes (e-cigarettes) to attempt to quit, despite a lack of data concerning their efficacy and safety for smoking cessation. METHODS: The Evaluating the Efficacy of E-Cigarette use for Smoking Cessation (E3) trial is a multicentre randomized controlled trial (NCT02417467) with a treatment period of 12 weeks and follow-up of 52 weeks. A total of 376 participants motivated to quit smoking were enrolled at 17 Canadian centres (November 2016 to September 2019). Participants were randomized (1:1:1) to 1 of 3 treatment arms: nicotine e-cigarettes, non-nicotine e-cigarettes, or no e-cigarettes. All groups received individual counselling. Treatment allocation was double-blind for the e-cigarette groups. The trial includes follow-ups by telephone at weeks 1, 2, 8, and 18, and clinic visits at weeks 4, 12, 24, and 52. The primary endpoint is to compare nicotine e-cigarettes to counselling alone in terms of biochemically validated point-prevalence smoking abstinence at 12 weeks; the primary endpoint was changed from 52 weeks after early termination (77% of targeted enrollment) due to a prolonged delay in e-cigarette manufacturing. The secondary objectives are to examine the efficacy of nicotine and non-nicotine e-cigarettes in terms of point-prevalence and continuous smoking abstinence, and reduction in daily cigarette consumption at all follow-ups through week 52, and to describe the occurrence of adverse events. CONCLUSION: The E3 trial will provide regulators, health care professionals, and smokers with important information about the efficacy and safety of e-cigarettes for smoking cessation.

CONTEXTE: Le sevrage tabagique améliore la morbidité et la mortalité chez les fumeurs qui parviennent à une abstinence à long term. De nombreux fumeurs utilisent des cigarettes électroniques (e-cigarettes) pour tenter d'arrêter de fumer, malgré le manque de données concernant leur efficacité et leur sécurité pour le sevrage tabagique. MÉTHODES: L'essai "Evaluation l'utilisation de la cigarette Électronique (E3)" pour cesser de fumer (E3)" est un essai contrôlé randomisé multicentrique (NCT02417467) avec une période de traitement de 12 semaines et un suivi de 52 semaines. Au total, 376 participants motivés à cesser de fumer ont été inscrits par 17 centres canadiens (de novembre 2016 à septembre 2019). Les participants ont été randomisés (1:1:1) dans l'un des trois groupes de traitement : e-cigarettes à la nicotine, e-cigarettes sans nicotine ou sans e-cigarette. Tous les groupes ont bénéficié de conseils individuels. Pour les groups avec une e-cigarettes, l'attribution des traitements a été faite en double aveugle. L'essai comprend de suivis par téléphone aux semaines 1, 2, 8 et 18, et des visites à la clinique aux semaines 4, 12, 24 et 52. L'objectif principal est de comparer les e-cigarettes nicotinique au conseils seul, en termes d'abstinence tabagique ponctuelle de 7 jours confirmée par un indicateur biochimique validée à 12 semaines; changé de la 52 semaines en raison d'une fin anticipée (77 % des inscriptions ciblées) dû à un retard prolongé dans la fabrication des e-cigarettes. Les objectifs secondaires sont d'examiner l'efficacité des e-cigarettes à la nicotine et sans nicotine en termes de prévalence ponctuelle et de sevrage tabagique continu, et la réduction quotidienne de cigarettes consommer pour l'ensemble des suivis jusqu'à la semaine 52, et de décrire l'occurrence des effets indésirables. CONCLUSION: L'essai E3 fournira aux régulateurs, aux professionnels de la santé et aux fumeurs des informations importantes sur l'efficacité et la sécurité des e-cigarettes pour le sevrage tabagique.

Cholesteryl Ester Transfer Protein Inhibitors and Cardiovascular Outcomes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Cholesteryl ester transfer protein (CETP) inhibitors increase serum high-density lipoprotein cholesterol (HDL-c) concentration; however, their impact on cardiovascular outcomes is not clear. This systematic review examines the effect of CETP inhibitors on serum lipid profiles, cardiovascular events, and all-cause mortality. METHODS: We searched MEDLINE, Embase, and the Cochrane Library of Clinical Trials for placebo-controlled randomized controlled trials (RCTs) that examined the effect of a CETP inhibitor (dalcetrapib, anacetrapib, evacetrapib, or TA-8995) on all-cause mortality, major adverse cardiovascular events (MACE), or the components of MACE at ≥6 months. Data were pooled using random-effects models. RESULTS: A total of 11 RCTs (n = 62,431) were included in our systematic review; 4 examined dalcetrapib (n = 16,612), 6 anacetrapib (n = 33,682), and 1 evacetrapib (n = 12,092). Compared to dalcetrapib, ana-cetrapib and evacetrapib were more efficacious at raising HDL-c levels (∼100-130 vs. ∼30%). Anacetrapib and evacetrapib also decreased low-density lipoprotein cholesterol (LDL-c) by approximately 30% while dalcetrapib did not affect the LDL-c level. Overall, CETP inhibitors were not associated with the incidence of MACE (pooled relative risk [RR]: 0.97; 95% confidence interval [CI]: 0.91-1.04). CETP inhibitors may decrease the risks of nonfatal myocardial infarction (MI) (RR: 0.93; 95% CI: 0.87-1.00) and cardiovascular death (RR: 0.92; 95% CI: 0.83-1.01), though these trends did not reach statistical significance. CONCLUSIONS: CETP inhibitors are not associated with an increased risk of MACE or all-cause mortality. There is a trend towards small reductions in nonfatal MI and cardiovascular death, though the clinical im-portance of such reductions is likely modest.

Meta-Analysis of Transcatheter Versus Surgical Aortic Valve Replacement in Low Surgical Risk Patients.

Current guidelines recommend transcatheter aortic valve implantation (TAVI) for patients with severe aortic stenosis at elevated surgical risk, but not for patients at low surgical risk. Our objective is to compare major clinical outcomes and procedural complications with TAVI versus surgical aortic valve replacement in patients with severe aortic stenosis at low surgical risk. We conducted a systematic review and meta-analysis of randomized controlled trials, identified through a systematic search of the MEDLINE, Embase, and Cochrane databases. Count data were pooled across trials using random-effects models with inverse variance weighting to obtain relative risks (RRs) and corresponding 95% confidence intervals (CIs). Three randomized controlled trials (n = 2,629) were included. At 30 days, TAVI was associated with a substantial reduction in all-cause mortality (RR: 0.45, 95%CI: 0.20 to 0.99), atrial fibrillation (RR: 0.27, 95%CI: 0.17 to 0.41), life threatening/disabling bleeding (RR: 0.29, 95%CI: 0.12 to 0.69), and acute kidney injury (RR: 0.28, 95%CI: 0.14 to 0.57). The reduction in atrial fibrillation persisted at 12 months (RR: 0.32, 95%CI: 0.21 to 0.49). However, TAVI patients had an increased risk of permanent pacemaker implantation at both 30 days (RR: 3.13, 95%CI: 1.36 to 7.21) and 12 months (RR: 2.99, 95%CI: 1.19 to 7.51). Due to the low absolute numbers of events, results were inconclusive at 30 days and 12 months for cardiovascular mortality, stroke, transient ischemic attack, and myocardial infarction. In conclusion, while some outcomes remained inconclusive, these data suggest that TAVI should be considered as a first-line therapy for the treatment of severe aortic stenosis in low surgical risk patients.

E-cigarettes and youth: Patterns of use, potential harms, and recommendations.

Electronic cigarette (e-cigarette) use has risen to unprecedented levels among youth in the United States. In this review, we discuss the patterns of use underlying the current youth vaping epidemic, potential harms from e-cigarette use, and the regulatory, public health, and clinical responses to e-cigarette use among youth. Between 2017 and 2018, past 30-day use of nicotine e-cigarettes among high school seniors nearly doubled, from 11% to 21%, representing the largest recorded increase for any adolescent substance use in over four decades. There are concerns that e-cigarette use could renormalize smoking behaviors, lead to the uptake of conventional cigarette use by youth, and have adverse effects in the developing brain and lungs of adolescents. Prevention and harm reduction efforts thus far have focused on policies to prevent youth access to vaping products and on public health strategies to expose the risks of youth vaping. However, it remains unclear if ongoing initiatives are sufficient to curb e-cigarette use by youth. Most health professionals agree that youth exposure to e-cigarettes needs to be addressed but feel uninformed, rely on unconventional information sources such as the media and their patients, and report that routine screening procedures concerning e-cigarettes are lacking. A coordinated effort from policy makers, public health agencies, parents, educators, health practitioners, and researchers is essential to mitigate harms from e-cigarette use in this vulnerable population.