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.

Feasibility of restricting e-cigarettes to prescription only for smoking cessation.

E-cigarette use among youth in Canada has risen to epidemic proportions. E-cigarettes are also moderately useful smoking cessations aids. Restricting e-cigarettes to prescription only smoking cessation aids could help limit youth's access to them while keeping them available as therapies for patients who smoke conventional cigarettes. In Canada, drugs or devices must be approved by regulatory bodies such as Health Canada in order to become licensed prescription medications. A similar situation is underway in Australia, where e-cigarettes have been restricted to prescription only. This commentary explores the feasibility of a similar regulation for e-cigarettes in Canada as prescription smoking cessation aids.

Evaluating non-cognitive skills in medical school applicants.

Medical school candidates must have both the cognitive and professional competencies required to become good physicians. In this commentary, we outline the evidence and outcomes associated with the implementation of these selection methodologies and evaluate their ability to assess non-cognitive skills.

Gender Disparities in Academic Outcomes Among Graduates of a Canadian MD-PhD Program.

PURPOSE: Women have traditionally been underrepresented in MD and MD-PhD training programs. Here, we describe the changing demographics of an MD-PhD Program over three distinct time intervals. METHODS: We designed a 64-question survey and sent it to 47 graduates of the McGill University MD-PhD program in Montréal, Québec, Canada, since its inception in 1985. We also sent a 23-question survey to the 24 students of the program in 2021. The surveys included questions related to demographics, physician-scientist training, research metrics, as well as academic and personal considerations. RESULTS: We collected responses from August 2020 to August 2021 and grouped them into three intervals based on respondent graduation year: 1995-2005 (n = 17), 2006-2020 (n = 23) and current students (n = 24). Total response rate was 90.1% (n = 64/71). We found that there are more women currently in the program compared to the 1995-2005 cohort (41.7% increase, p<0.01). In addition, women self-reported as physician-scientists less frequently than men and reported less protected research time. CONCLUSIONS: Overall, recent MD-PhD alumni represent a more diverse population compared with their earlier counterparts. Identifying barriers to training remains an important step in ensuring MD-PhD trainees become successful physician-scientists.

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.

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.

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.

An exercise in scientific writing for physicians in training.

It is important to strengthen critical thinking and scientific writing abilities during medical training to support trainees in their research endeavors and prepare students for careers in academic medicine. This commentary describes an interactive workshop to encourage student engagement with scientific literature and contribution to scholarly discourse by writing letters to the editor (LTEs). Students in the MD-PhD program at McGill University were asked to identify an article from a high-impact journal and think about ways in which they could address its scientific content. Students completed this preparation on their own time and then attended a 90-minute workshop where their LTEs were finalized and submitted. The LTE workshops were conducted in 2017 and 2019, and student participation and informal feedback indicated that perceptions of the workshops were positive. The workshops provided students an opportunity to strengthen their critical appraisal and academic communication skills while also contributing to the scientific literature. Letters written by aspiring and practicing physicians add valuable clinical insight to the literature and promote physician engagement with research. Strategies to support the adoption of LTE workshops include incorporating them into longitudinal curricula in medical school and integrating them into journal clubs during residency or fellowship.

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.

The effectiveness and safety of the Impella ventricular assist device for high-risk percutaneous coronary interventions: A systematic review.

BACKGROUND: Small randomized controlled trials (RCTs) and observational studies have examined the effectiveness and safety of the Impella device, a percutaneous left ventricular assist device, in the setting of high-risk percutaneous coronary intervention (PCI). However, data are sparse and results are conflicting. Our objective was to evaluate the effectiveness and safety of the Impella device in high-risk patients undergoing PCI via a systematic review of the literature. METHODS: We searched Medline, EMBASE, and the Cochrane Library for RCTs and observational studies that evaluated the Impella device in high-risk patients undergoing PCI. Inclusion was restricted to studies in which ≥10 patients received the Impella device; both uncontrolled and controlled (versus intra-aortic-balloon pump [IABP]) studies were included. RESULTS: A total of 20 studies (4 RCTs, 2 controlled observational studies, and 14 uncontrolled observational studies; 1,287 patients) were included, with follow-up ranging from 1 to 42 months. The use of Impella resulted in improved procedural and hemodynamic characteristics in controlled and uncontrolled studies. In controlled studies, the 30-day rates of all-cause mortality and MACE were similar across groups. In most uncontrolled studies, the 30-day rates of all-cause mortality were generally low (range: 3.7%-10%), though rates of MACE were slightly higher (range: 5%-20%). CONCLUSION: The Impella device was found to improve procedural and hemodynamic parameters, but only limited randomized data are available regarding clinical outcomes associated with its use. Large, multicenter RCTs are needed to definitively establish the effectiveness of the Impella device among high-risk PCI patients.

2018 ACC/HRS/NASCI/SCAI/SCCT Expert Consensus Document on Optimal Use of Ionizing Radiation in Cardiovascular Imaging-Best Practices for Safety and Effectiveness, Part 2: Radiological Equipment Operation, Dose-Sparing Methodologies, Patient and Medical Personnel Protection.

The stimulus to create this document was the recognition that ionizing radiation-guided cardiovascular procedures are being performed with increasing frequency, leading to greater patient radiation exposure and, potentially, to greater exposure to clinical personnel. While the clinical benefit of these procedures is substantial, there is concern about the implications of medical radiation exposure. ACC leadership concluded that it is important to provide practitioners with an educational resource that assembles and interprets the current radiation knowledge base relevant to cardiovascular procedures. By applying this knowledge base, cardiovascular practitioners will be able to select procedures optimally, and minimize radiation exposure to patients and to clinical personnel. "Optimal Use of Ionizing Radiation in Cardiovascular Imaging - Best Practices for Safety and Effectiveness" is a comprehensive overview of ionizing radiation use in cardiovascular procedures and is published online. To provide the most value to our members, we divided the print version of this document into 2 focused parts. "Part I: Radiation Physics and Radiation Biology" addresses radiation physics, dosimetry and detrimental biologic effects. "Part II: Radiologic Equipment Operation, Dose-Sparing Methodologies, Patient and Medical Personnel Protection" covers the basics of operation and radiation delivery for the 3 cardiovascular imaging modalities (x-ray fluoroscopy, x-ray computed tomography, and nuclear scintigraphy). For each modality, it includes the determinants of radiation exposure and techniques to minimize exposure to both patients and to medical personnel.

2018 ACC/HRS/NASCI/SCAI/SCCT Expert Consensus Document on Optimal Use of Ionizing Radiation in Cardiovascular Imaging-Best Practices for Safety and Effectiveness, Part 1: Radiation Physics and Radiation Biology: A Report of the American College of Cardiology Task Force on Expert Consensus Decision Pathways Developed in Collaboration With Mended Hearts.

The stimulus to create this document was the recognition that ionizing radiation-guided cardiovascular procedures are being performed with increasing frequency, leading to greater patient radiation exposure and, potentially, to greater exposure for clinical personnel. Although the clinical benefit of these procedures is substantial, there is concern about the implications of medical radiation exposure. The American College of Cardiology leadership concluded that it is important to provide practitioners with an educational resource that assembles and interprets the current radiation knowledge base relevant to cardiovascular procedures. By applying this knowledge base, cardiovascular practitioners will be able to select procedures optimally, and minimize radiation exposure to patients and to clinical personnel. Optimal Use of Ionizing Radiation in Cardiovascular Imaging: Best Practices for Safety and Effectiveness is a comprehensive overview of ionizing radiation use in cardiovascular procedures and is published online. To provide the most value to our members, we divided the print version of this document into 2 focused parts. Part I: Radiation Physics and Radiation Biology addresses the issue of medical radiation exposure, the basics of radiation physics and dosimetry, and the basics of radiation biology and radiation-induced adverse effects. Part II: Radiological Equipment Operation, Dose-Sparing Methodologies, Patient and Medical Personnel Protection covers the basics of operation and radiation delivery for the 3 cardiovascular imaging modalities (x-ray fluoroscopy, x-ray computed tomography, and nuclear scintigraphy) and will be published in the next issue of the Journal.

Smoking abstinence 1 year after acute coronary syndrome: follow-up from a randomized controlled trial of varenicline in patients admitted to hospital.

BACKGROUND: Patients who continue to smoke after acute coronary syndrome are at increased risk of reinfarction and death. We previously found use of varenicline to increase abstinence 24 weeks after acute coronary syndrome; here we report results through 52 weeks. METHODS: The EVITA trial was a multicentre, double-blind, randomized, placebo-controlled trial of varenicline for smoking cessation in patients admitted to hospital with acute coronary syndrome. Participants were randomly assigned (1:1) to receive varenicline or placebo for 12 weeks, in conjunction with low-intensity counselling. Smoking abstinence was assessed via 7-day recall, with biochemical validation using exhaled carbon monoxide. Participants lost to follow-up or withdrawn were assumed to have returned to smoking. RESULTS: Among the 302 participants, abstinence declined over the course of the trial, with 34.4% abstinent 52 weeks after acute coronary syndrome. Compared with placebo, point estimates suggest use of varenicline increased point-prevalence abstinence (39.9% v. 29.1%, difference 10.7%, 95% confidence interval [CI] 0.01% to 21.44%; number needed to treat 10), continuous abstinence (31.1% v. 21.2%, difference 9.9%, 95% CI -0.01% to 19.8%) and reduction in daily cigarette smoking by 50% or greater (57.8% v. 49.7%, difference 8.1%, 95% CI -3.1% to 19.4%). Varenicline and placebo groups had similar occurrence of serious adverse events (24.5% v. 21.9%, risk difference 2.7%, 95% CI -7.3% to 12.6%) and major adverse cardiovascular events (8.6% v. 9.3%, risk difference -0.7%, 95% CI -7.8% to 6.5%). INTERPRETATION: Varenicline was efficacious for smoking cessation in this high-risk patient population. However, 60% of patients who received treatment with varenicline still returned to smoking. Trial registration: ClinicalTrials.gov, no. NCT00794573.

Exposure to Low-Dose Ionizing Radiation From Cardiac Procedures in Patients With Congenital Heart Disease: 15-Year Data From a Population-Based Longitudinal Cohort.

BACKGROUND: The burden of low-dose ionizing radiation (LDIR) exposure from medical procedures among individuals with congenital heart disease (CHD) is unknown. In this longitudinal population-based study, we sought to determine exposure to LDIR-related cardiac imaging and therapeutic procedures in children and adults with CHD. METHODS AND RESULTS: In an analysis of the Quebec CHD database, exposure to the following LDIR-related cardiac procedures was recorded: catheter-based diagnostic procedures, structural heart interventions, coronary interventions, computed tomography scans of the chest, nuclear procedures, and pacemaker/implantable cardioverter-defibrillator insertion and repair. From 1990 to 2005, there were 16 253 LDIR-exposed patients with CHD with 317 988 patient-years of available follow-up. The total number of LDIR-related procedures increased from 18.5 to 51.9 per 1000 CHD patients per year (P<0.0001). This increase was attributable to increases in rates per 1000 CHD patients in diagnostic cardiac catheterizations (11.7 to 13.7 per 1000), structural heart interventions (1.0 to 5.2 per 1000), coronary interventions (1.0 to 2.4 per 1000), pacemaker/implantable cardioverter-defibrillator insertions (1.6 to 4.4 per 1000), nuclear procedures (4.2 to 13.8 per 1000), and computed tomography scans of the chest (2.5 to 12.3 per 1000). Over time, among children with CHD, the median age at first LDIR procedure decreased from 5.0 years to 9.6 months. Severity of CHD significantly predicted extent of exposure. CONCLUSIONS: From 1990 to 2005, patients with CHD were exposed to increasing numbers of LDIR-emitting cardiac procedures. This exposure occurred at progressively younger ages. These findings provide an important perspective on longitudinal LDIR exposure in this at-risk population.

Varenicline for Smoking Cessation in Hospitalized Patients With Acute Coronary Syndrome.

BACKGROUND: Less than one-third of smokers hospitalized with an acute coronary syndrome (ACS) remain abstinent following discharge. We assessed whether varenicline, begun in-hospital, is efficacious for smoking cessation following ACS. METHODS AND RESULTS: We conducted a multi-center, double-blind, randomized, placebo-controlled trial in which smokers hospitalized with an ACS were randomized to varenicline or placebo for 12 weeks. All patients received low-intensity counseling. The primary end point was point-prevalence smoking abstinence assessed at 24 weeks by 7-day recall and biochemical validation using expired carbon monoxide. A total of 302 patients were randomized (mean age 55±9 years; 75% male; 56% ST-segment elevation myocardial infarction; 38% non-ST-segment elevation myocardial infarction; 6% unstable angina). Patients smoked a mean of 21±11 cigarettes/d at the time of hospitalization and had been smoking for a mean of 36±12 years. At 24 weeks, patients randomized to varenicline had significantly higher rates of smoking abstinence and reduction than patients randomized to placebo. Point-prevalence abstinence rates were 47.3% in the varenicline group and 32.5% in the placebo group (P=0.012; number needed to treat=6.8). Continuous abstinence rates were 35.8% and 25.8%, respectively (P=0.081; number needed to treat=10.0), and rates of reduction ≥50% in daily cigarette consumption were 67.4% and 55.6%, respectively (P=0.05; number needed to treat=8.5). Adverse event rates within 30 days of study drug discontinuation were similar between groups (serious adverse events: varenicline 11.9%, placebo 11.3%; major adverse cardiovascular events: varenicline 4.0%, placebo 4.6%). CONCLUSIONS: Varenicline, initiated in-hospital following ACS, is efficacious for smoking cessation. Future studies are needed to establish safety in these patients. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00794573.

Carotid Stenting Versus Endarterectomy for Asymptomatic Carotid Artery Stenosis: A Systematic Review and Meta-Analysis.

BACKGROUND AND PURPOSE: There is no consensus on the comparative efficacy and safety of carotid artery stenting (CAS) versus carotid endarterectomy (CEA) in patients with asymptomatic carotid artery stenosis. To evaluate CAS versus CEA in asymptomatic patients, we conducted a systematic review and meta-analysis of randomized controlled trials. METHODS: We systematically searched EMBASE, PubMed, MEDLINE, and the Cochrane Library for randomized controlled trials comparing CAS to CEA in asymptomatic patients using a pre-specified protocol. Two independent reviewers identified randomized controlled trials meeting our inclusion/exclusion criteria, extracted relevant data, and assessed quality using the Cochrane risk of bias tool. Random effects models with inverse-variance weighting were used to estimate pooled risk ratios (RRs) comparing the incidences of periprocedural and long-term outcomes between CAS and CEA. RESULTS: We identified 11 reports of 5 randomized controlled trials for inclusion (n=3019) asymptomatic patients. The pooled incidences of any periprocedural stroke (RR, 1.84; 95% confidence interval [CI], 0.99-3.40), periprocedural nondisabling stroke (RR, 1.95; 95% CI, 0.98-3.89), and any periprocedural stroke or death (RR, 1.72; 95% CI, 0.95-3.11) trended toward an increased risk after CAS. We could not rule out clinically significant differences between treatments for long-term stroke (RR, 1.24; 95% CI, 0.76-2.03) and the composite outcome of periprocedural stroke, death or myocardial infarction, or long-term ipsilateral stroke (RR, 0.92; 95% CI, 0.70-1.21). CONCLUSIONS: Although uncertainty surrounds the long-term outcomes of CAS versus CEA, the potential for increased risks of periprocedural stroke and periprocedural stroke or death with CAS suggests that CEA is the preferred option for the management of asymptomatic carotid stenosis.

Defining optimal activated clotting time for percutaneous coronary intervention: A systematic review and Bayesian meta-regression.

BACKGROUND: Guidelines recommend routine monitoring of unfractionated heparin (UFH) with activated clotting time (ACT) during percutaneous coronary intervention (PCI). However, the optimal ACT for patients undergoing PCI is unclear. METHODS: We sought to determine the association of peak ACT during PCI with 30-day major adverse cardiac events (MACE; all-cause mortality, myocardial infarction, and revascularization) and bleeding events. We searched the Cochrane Central Register of Controlled Trials, EMBASE, and Medline for randomized controlled trials (RCTs) evaluating UFH through May 2015. Only patients randomized to UFH alone or to UFH with a glycoprotein IIb/IIIa inhibitor (GPI) were analyzed using Bayesian meta-regression. RESULTS: Among 13 included RCTs (n = 17455), eight (n = 5521) included study arms of UFH alone and 12 (n = 11934) included arms of UFH with a GPI. Peak ACT ranged from 201 to 460 sec for UFH alone and 248-317 sec for UFH with a GPI. With UFH alone, the probability of MACE was 7.0% (95% credible interval [CrI] 1.5, 31.5) for a peak ACT of 200 sec and 5.8% (95% CrI 2.6, 12.0) for 300 sec. Among UFH with a GPI, the probability of MACE was 2.8% (95% CrI 0.8, 6.8) for a peak ACT of 200 sec and 7.2% (95% CrI 5.4, 9.7) for 300 sec. CONCLUSION: Among individual RCTs, the probability of MACE and major bleeding events associated with low versus high values of peak ACT is inconsistent. Our meta-regression results are inconclusive, emphasizing the need for RCTs comparing low versus high doses of UFH. © 2016 Wiley Periodicals, Inc.

Cessation treatment adherence and smoking abstinence in patients after acute myocardial infarction.

BACKGROUND: Previous trials examining the use of bupropion for smoking cessation therapy after myocardial infarction (MI) have been inconclusive. To understand better the observed lack of effectiveness of bupropion in this population, we examined abstinence rates by level of adherence across treatment groups. METHODS: We used data from a randomized, double-blind, placebo-controlled trial of bupropion in smokers (n = 388) hospitalized with MI to study the association of interest. Patients were classified as being fully adherent if they reported taking 2 pills/d; partially adherent if they reported 0, 1, and/or 2 pills/d; and nonadherent if they reported 0 and/or 1 pill/d throughout the 9-week treatment period. Abstinence was assessed by 7-day biochemically validated self-report at 4 and 9 weeks and 6 and 12 months. RESULTS: A total of 156 patients were fully adherent to the study medication (66 bupropion and 90 placebo), 149 were partially adherent (76 and 73, respectively), and 83 were nonadherent (46 and 37, respectively). Regardless of treatment group, patients who were fully or partially adherent reported greater abstinence than did nonadherent patients. Among partially adherent patients, bupropion conferred an important benefit at 12 months (% difference 13.3, 95% CI 1.3-25.3). At 12 months, patients who were fully adherent were more likely to be abstinent compared with those who were nonadherent (adjusted odds ratio 7.6, 95% CI 3.2-17.6). CONCLUSIONS: Adherence to study medication, regardless of assigned treatment, is associated with a substantial increase in abstinence. Patients who are motivated to quit smoking should be targeted for smoking cessation treatment after MI.