Optimal hepatitis C treatment adherence patterns and sustained virologic response among people who inject drugs: The HERO study.

BACKGROUND & AIMS: Direct-acting antivirals (DAAs) are highly effective for treating HCV infection even among people who inject drugs (PWID). Yet, little is known about patients' adherence patterns and their association with sustained virologic response (SVR) rates. We aimed to summarize various adherence patterns and determine their associations with SVR. METHODS: Electronic blister packs were used to measure daily adherence to once-a-day sofosbuvir/velpatasvir during the 12-week treatment period among active PWIDs. Blister pack data were available for 496 participants who initiated DAAs for whom SVR status was known. Adherence was summarized in multiple patterns, such as total adherent days, consecutive missed days, and early discontinuations. Thresholds for adherence patterns associated with >90% SVR rates were also determined. RESULTS: The overall SVR rate was 92.7%, with a median adherence rate of 75%. All adherence patterns indicating greater adherence were significantly associated with achieving SVR. Participant groups with ≥50% (>42/84) adherent days or <26 consecutive missed days achieved an SVR rate of >90%. Greater total adherent days during 9-12 weeks and no early discontinuation were significantly associated with higher SVR rates only in those with <50% adherence. Participants with first month discontinuation and ≥2 weeks of treatment interruption had low SVR rates, 25% and 85%, respectively. However, greater adherent days were significantly associated with SVR (adjusted odds ratio 1.10; 95% CI 1.04-1.16; p <0.001) even among participants with ≥14 consecutive missed days. CONCLUSIONS: High SVR rates can be achieved in the PWID population despite suboptimal adherence. Encouraging patients to take as much medication as possible, with <2 weeks consecutive missed days and without early discontinuation, was found to be important for achieving SVR. IMPACT AND IMPLICATIONS: People who inject drugs can be cured of HCV in >90% of cases, even with relatively low adherence to direct-acting antivirals, but early discontinuations and long treatment interruptions can significantly reduce the likelihood of achieving cure. Clinicians should encourage people who inject drugs who are living with HCV to adhere daily to direct-acting antivirals as consistently as possible, but if any days are interrupted, to continue and complete treatment. These results from the HERO study are important for patients living with HCV, clinicians, experts writing clinical guidelines, and payers. CLINICAL TRIAL NUMBER: NCT02824640.

Overreporting of adherence to hepatitis C direct-acting antiviral therapy and sustained virologic response among people who inject drugs in the HERO study.

BACKGROUND: Self-reported adherence to direct-acting antivirals (DAAs) to treat hepatitis C virus (HCV) among persons who inject drugs (PWID) is often an overreport of objectively measured adherence. The association of such overreporting with sustained virologic response (SVR) is understudied. This study among PWID aimed to determine a threshold of overreporting adherence that optimally predicts lower SVR rates, and to explore correlates of the optimal overreporting threshold. METHODS: This study analyzed per-protocol data of participants with adherence data (N = 493) from the HERO (Hepatitis C Real Options) study. Self-reported and objective adherence to a 12-week DAA regimen were measured using visual analogue scales and electronic blister packs, respectively. The difference (Δ) between self-reported and objectively measured adherence was calculated. We used the Youden index based on receiver operating characteristic (ROC) curve analysis to identify an optimal threshold of overreporting for predicting lower SVR rates. Factors associated with the optimal threshold of overreporting were identified by comparing baseline characteristics between participants at/above versus those below the threshold. RESULTS: The self-reported, objective, and Δ adherence averages were 95.1% (SD = 8.9), 75.9% (SD = 16.3), and 19.2% (SD = 15.2), respectively. The ≥ 25% overreporting threshold was determined to be optimal. The SVR rate was lower for ≥ 25% vs. < 25% overreporting (86.7% vs. 95.8%, p <.001). The factors associated with ≥ 25% Δ adherence were unemployment; higher number of days and times/day of injecting drugs; higher proportion of positive urine drug screening for amphetamine, methamphetamine, and oxycodone, and negative urine screening for THC (tetrahydrocannabinol)/cannabis. CONCLUSIONS: Self-reported DAA adherence was significantly greater than objectively measured adherence among PWID by 19.2%. Having ≥ 25% overreported adherence was associated with optimal prediction of lower SVR rates. PWID with risk factors for high overreporting may need to be more intensively managed to promote actual adherence.

A Video-Observed Treatment Strategy to Improve Adherence to Treatment Among Persons Who Inject Drugs Infected With Hepatitis C Virus: Qualitative Study of Stakeholder Perceptions and Experiences.

BACKGROUND: Direct-acting antiviral medications have the potential to eliminate the hepatitis C virus (HCV) epidemic among people who inject drugs; yet, suboptimal adherence remains a barrier. Directly observed treatment (DOT), an effective strategy for optimizing adherence, has been frequently implemented in opioid treatment programs but less commonly in community health settings due to the heavy burden of daily visits. An alternative is video-observed therapy (VOT), which uses mobile health technology to monitor adherence. VOT has not been widely studied among people who inject drugs with HCV. OBJECTIVE: This qualitative study, part of a larger implementation evaluation, investigates stakeholder perceptions and experiences with VOT in Project HERO (Hepatitis C Real Outcomes), a multisite pragmatic trial testing treatment delivery models for people who inject drugs with HCV. Our goal was to understand the potential barriers and facilitators to the implementation of the VOT technology. METHODS: Qualitative interviews were conducted with 27 Project HERO study staff and 7 patients. Interviews focused on perceptions and experiences with the VOT app and barriers and facilitators to implementation. Team meeting minutes over the first 2 years of the project were transcribed. A coding system was developed and applied to the data. We summarized thematic data and compared participant perceptions to generate a close understanding of the data. RESULTS: Frequent barriers to VOT included mechanical failure, stolen or lost phones, and a steep learning curve for participants and study staff. In sites with older and less technically skilled participants, staff found it difficult to implement the VOT app. Research staff found that the routine monitoring of app use led to closer engagement with participants. This was both a benefit and a potential threat to the validity of this pragmatic trial. Patient participants reported mixed experiences. CONCLUSIONS: VOT may be a useful alternative to DOT for some patients, but it may not be feasible for all. Significant staff involvement may be required.

Changes in Health-related Quality of Life for Hepatitis C Virus-Infected People Who Inject Drugs While on Opioid Agonist Treatment Following Sustained Virologic Response.

BACKGROUND: Although efforts to treat hepatitis C virus (HCV) in people who inject drugs (PWID) yield high rates of sustained virologic response (SVR), the relationship between successful HCV treatment and health-related quality of life (HRQOL) among PWID is poorly understood. We examined HRQOL changes throughout HCV treatment and post-treatment for PWID achieving SVR. METHODS: Participants included 141 PWID who achieved SVR following HCV treatment onsite at 3 opioid agonist treatment (OAT) clinics in the Bronx, New York. EQ-5D-3L assesses 5 health dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), producing an index of HRQOL ranging from 0 to 1. EQ-5D-3L was measured at baseline; 4, 8, and 12 weeks during treatment; and 12 and 24 weeks post-treatment. Linear mixed effects regression models assessed changes in the mean EQ-5D-3L index over time. RESULTS: Mean EQ-5D-3L index baseline was 0.66 (standard error [SE] = 0.02). While over half the population reported no baseline problems with self-care (85.1%), usual activities (56.0%), and mobility (52.5%), at least two-thirds reported problems with pain/discomfort (78.0%) and anxiety/depression (66.0%). Twenty-four weeks post-treatment, proportions reporting pain/discomfort and anxiety/depression decreased by 25.7% and 24.0%, respectively. Mean EQ-5D-3L index significantly improved during treatment (P < .0001), and improvement was sustained following treatment completion, with mean EQ-5D-3L index of 0.77 (SE = 0.02) 12 weeks post-SVR. CONCLUSIONS: HCV treatment led to sustained improvement in HRQOL for PWID on OAT who achieved SVR. Future research is necessary to determine whether improvements in HRQOL can be sustained beyond 12 weeks post-SVR.

Changes in alcohol use during hepatitis C treatment in persons who inject drugs.

People who inject drugs (PWID) are a vulnerable population at high risk for acquiring hepatitis C virus (HCV) and frequently suffer from comorbid alcohol use. This study examines the characteristics and correlates of alcohol use among study participants, the association between alcohol consumption and sustained virologic response (SVR) in patients receiving HCV treatment, changes in drinking behaviours during HCV treatment and associations of drinking over time with specific models of HCV treatment. Participants were 150 PWID with HCV who were receiving opioid agonist therapy (OAT) and enrolled in a randomized clinical trial exploring the effectiveness of three models of care for HCV treatment. The addiction severity index was the primary measure of alcohol consumption. Days of alcohol intake were evaluated longitudinally and across three treatment groups. At baseline, 31% (47/150) reported having at least one drink in the last 30 days including 24% (36/150) who reported drinking to intoxication in the last 30 days. There was no difference in SVR rates between groups. There was a significant decrease in overall days of drinking from baseline (7.78 ± 7.86) to follow-up at Week 24 (5.78 ± 8.83) (p = 0.041), but there were no significant changes among those who drank to intoxication; modified directly observed therapy (mDOT) was the only group with a significant decline in days of alcohol consumption (p = 0.041). In this cohort of PWID on OAT, baseline alcohol consumption did not affect SVR rates. HCV treatment was overall associated with decreased alcohol consumption. In particular, mDOT was associated with decreased alcohol consumption. Given the additive effect of alcohol and HCV on the development of cirrhosis, studies should be done to investigate the complimentary effects of the mDOT model of care on alcohol cessation.

Longitudinal associations between U.S. youth exposure to E-cigarette marketing and E-cigarette use harm perception and behavior change.

E-cigarette marketing tactics to reach and appeal to youth are rapidly changing. This study examined to what extent youth e-cigarette marketing exposure was associated with e-cigarette use behavior change one year later, during a time when youth e-cigarette use was starting to surge in the U.S. Using nationally representative longitudinal public-use data from the Population Assessment of Tobacco and Health (PATH) Study, we examined associations between recalled e-cigarette marketing exposure (2016-2018) at Wave (W) 4 and e-cigarette use harm perception and behavior change (ever, current, and regular use) one year later (W4.5; 2017-2018) among W4 never tobacco users (n = 9405). Recall of exposure to e-cigarette marketing through different channels was also examined in multivariable models controlling for socio-demographic factors and established e-cigarette use risk factors. Results show that the most frequently recalled channels of e-cigarette marketing exposure were retail stores (50.3%), television (22.2%), and websites/social media (20.2%). Over one year, 21.2%, 7.8%, 3.4%, and 1.2% of respondents reported reduced harm perceptions, and ever, current, and regular use of e-cigarettes, respectively, at follow-up. Recalled exposure to e-cigarette marketing was associated with reduced e-cigarette harm perception (AOR = 1.20; 95% CI = 1.05-1.37) and ever (AOR = 1.26; 95% CI = 1.01-1.56) and current use (AOR = 1.40; 95% CI = 1.02-1.92) at follow-up. E-cigarette marketing exposure through websites/social media was associated with reduced harm perceptions and all stages of e-cigarette use change, including regular use. Identifying marketing techniques and channels that change youth e-cigarette harm perceptions and influence e-cigarette use progression is essential to inform e-cigarette regulatory policies and prevention campaigns.

Developing a European network of analytical laboratories and government institutions to prevent poisoning of raptors.

Many cases of wildlife poisoning in Europe have been reported causing population declines, especially in raptors. Toxicovigilance and risk assessment studies are essential to reinforce the knowledge of the number of illegal poisoning cases and the substances involved in these crimes. Many researchers and projects in different institutions have suggested the creation of a network to improve communication and share information between European countries. This article presents the results of the Short-Term Scientific Mission titled "Developing a Network of Analytical Labs and Government Institutions" supported by the COST Action European Raptor Biomonitoring Facility (CA16224), which aims to initiate a network of veterinary forensic toxicology laboratories, in order to improve communication among laboratories to prevent wildlife poisoning, especially in raptors. For this purpose, a questionnaire was designed and sent by email to 119 laboratories in Europe. It contained 39 questions on different topics (e.g. laboratory activities, analytical information). A total of 29 responses were received. Most participant laboratories work on veterinary forensic toxicology research and external cases at the same time, which provides a robust overview of the actual situation in the field. Analytical techniques and data collection methods should be harmonised, and communication between laboratories is encouraged to create a more effective network. The present study established contact between laboratories as an initial step to create a European network and compiled basic data to identify strengths and weaknesses that will help harmonise methodologies across Europe and increase pan-European capacities.

Hepatitis C Virus Direct-Acting Antiviral Treatment Adherence Patterns and Sustained Viral Response Among People Who Inject Drugs Treated in Opioid Agonist Therapy Programs.

BACKGROUND: Adequate medication adherence is critical for achieving sustained viral response (SVR) of hepatitis C virus (HCV) among people who inject drugs (PWID). However, it is less known which patterns of direct-acting antiviral (DAA) treatment adherence are associated with SVR in this population or what factors are associated with each pattern. METHODS: The randomized 3-arm PREVAIL study used electronic blister packs to obtain daily time frame adherence data in opiate agonist therapy program settings. Exact logistic regressions were applied to test the associations between SVR and 6 types of treatment adherence patterns. RESULTS: Of the 113 participants treated with combination DAAs, 109 (96.5%) achieved SVR. SVR was significantly associated with all pattern parameters except for number of switches between adherent and missed days: total adherent daily doses (exact adjusted odds ratio [AOR] = 1.12; 95% confidence interval [CI] = 1.04-1.22), percent total doses (1.09; 1.03-1.16), days on treatment (1.16; 1.05-1.32), maximum consecutive adherent days (1.34; 1.06-2.04), and maximum consecutive nonadherent days (0.85; .74-.95 = 0.003). SVR was significantly associated with total adherent doses in the first 2 months of treatment, it was not in the last month. While alcohol intoxication was significantly associated with frequent switches, drug use was not associated with any adherence pattern. CONCLUSIONS: Consistent maintenance of adequate total dose adherence over the entire course of HCV treatment is important in achieving SVR among PWID. Additional integrative addiction and medical care may be warranted for treating PWID who experience alcohol intoxication.

Rates of perfect self-reported adherence to direct-acting antiviral therapy and its correlates among people who inject drugs on medications for opioid use disorder: The PREVAIL study.

Adequate adherence to direct-acting antivirals (DAAs) for hepatitis C virus (HCV) is critical to attaining sustained virologic response (SVR). In this PREVAIL study's secondary analyses, we explored the association between self-reported and objective DAAs adherence among a sample of people who inject drugs (PWID) receiving medications for opioid use disorder (MOUD) (N = 147). Self-reported adherence was recoded 3 times during treatment (weeks 4, 8 and 12) using a visual analog scale (VAS), whereas objective adherence was collected continuously during treatment using electronic blister packs. Participants who reported being perfectly adherent had significantly higher blister pack adherence in each period (weeks 4, 8 and 12; ps < .05) and over the 12-week study (p < .001) compared to those who reported being non-perfectly adherent. Whites were more likely to report perfect adherence (91.7%) than Blacks (48.7%), Latinos (52.2%) and other (75.0%) race groups. Participants who reported recent use of cocaine (63.9%) or polysubstance use (60.0%) and those who had a positive result for cocaine (62.8%) were more likely to be non-perfectly adherent, although none of these factors were associated with blister pack adherence. This study showed that the VAS could serve as a reliable option for assessing DAAs adherence among PWID on MOUD. The implementation of VAS may be an ideal option for monitoring adherence among PWID on MOUD, especially in clinical settings with limited resources. PWID on MOUD who are Black or other races than White, as well as those who report recent cocaine or polysubstance use may require additional support to maintain optimal DAA adherence.

Wildlife poisoning: a novel scoring system and review of analytical methods for anticoagulant rodenticide determination.

Anticoagulant rodenticides (ARs) are commonly used to control rodent populations and frequently involved in wildlife and domestic animal poisoning. These poisoning cases (especially for ARs) are a challenge for forensic toxicologists, and adequate post-mortem examination and toxicological analyses become essential for a proper diagnosis. Publications describing different analytical methods for AR analysis in biological samples are growing, and a clear compilation of the overall picture is needed to standardize methodologies in future research. This review aims to compile and compare the analytical procedures applied for AR determination in the literature. Using this information, a scoring system was developed for those techniques using liver and blood as matrices, and the techniques were ranked considering different criteria (i.e. sample amount required, recoveries, limits of quantification (LOQs), number of ARs analysed, points of the calibration curve and multi-class methods). This review shows an overview of the main methods used for AR analysis in forensic toxicology and will help to elucidate future directions to improve multi-residue techniques to detect the ARs involved in wildlife lethal poisoning.

Factors and HCV treatment outcomes associated with smoking among people who inject drugs on opioid agonist treatment: secondary analysis of the PREVAIL randomized clinical trial.

BACKGROUND: Cigarette smoking has emerged as a leading cause of mortality among people with hepatitis C virus (HCV). People who inject drugs (PWID) represent the largest group of adults infected with HCV in the US. However, cigarette smoking remains virtually unexplored among this population. This study aimed at (1) determining prevalence and correlates of cigarette smoking among HCV-infected PWID enrolled in opiate agonist treatment programs; (2) exploring the association of smoking with HCV treatment outcomes including adherence, treatment completion and sustained virologic response (SVR); and 3) exploring whether cigarette smoking decreased after HCV treatment. METHODS: Participants were 150 HCV-infected PWID enrolled in a randomized clinical trial primarily designed to test three intensive models of HCV care. Assessments included sociodemographics, presence of chronic health and psychiatric comorbidities, prior and current drug use, quality of life, and HCV treatment outcomes. RESULTS: The majority of the patients (84%) were current cigarette smokers at baseline. There was a high prevalence of psychiatric and medical comorbidities in the overall sample of PWID. Alcohol and cocaine use were identified as correlates of cigarette smoking. Smoking status did not influence HCV treatment outcomes including adherence, treatment completion and SVR. HCV treatment was not associated with decreased cigarette smoking. CONCLUSIONS: The present study showed high prevalence of cigarette smoking among this population as well as identified correlates of smoking, namely alcohol and cocaine use. Cigarette smoking was not associated with HCV treatment outcomes. Given the detrimental effects that cigarette smoking and other co-occurring, substance use behaviors have on HCV-infected individuals' health, it is imperative that clinicians treating HCV also target smoking, especially among PWID. The high prevalence of cigarette smoking among PWID will contribute to growing morbidity and mortality among this population even if cured of HCV. Tailored smoking cessation interventions for PWID along with HCV treatment may need to be put into clinical practice. TRIAL REGISTRATION: NCT01857245 . Registered May 20, 2013.

Mercury Exposure in Birds Linked to Marine Ecosystems in the Western Mediterranean.

Mercury (Hg), particularly as methylmercury (MeHg), is a nonessential, persistent, and bioaccumulative toxic element with high biomagnification capacity and is considered a threat to marine environments. We evaluated total Hg concentrations in liver, kidney, and brain in 62 individuals of 9 bird species linked to marine ecosystems from western Mediterranean admitted in a Wildlife Rehabilitation Center (WRC) (Alicante, Spain, 2005-2020). Age- and sex-related differences in Hg levels, as well as the cause of admission to the WRC, were also evaluated in certain species. The species studied were: northern gannet (Morus bassanus), European shag (Phalacrocorax aristotelis), great cormorant (Phalacrocorax carbo), osprey (Pandion haliaetus), Balearic shearwater (Puffinus mauretanicus), yellow-legged gull (Larus michahellis), razorbill (Alca torda), common tern (Sterna hirundo), and black-headed gull (Chroicocephalus ridibundus). Concentrations in feathers of 27 individuals, and concentrations in internal tissues in 7 other individuals of 7 different species were also reported but not statistically evaluated due to the limited number of samples. Results suggest that individuals were chronically exposed to Hg through diet. The differences in Hg concentrations among species may be explained by their diet habits. Mercury concentrations strongly correlated between tissues (r = 0.78-0.94, p < 0.001, n = 61-62). Some individuals of certain species (i.e., European shag, northern gannet, and great cormorant) showed Hg concentrations close to or above those described in the literature as causing reproductive alterations in other avian species. Consequently, certain individuals inhabiting western Mediterranean could be at risk of suffering long-term, Hg-related effects. Some of the species evaluated are listed within different categories of threat according to the International Union for Conservation of Nature (IUCN) and are endangered at a national level, so this study will provide valuable information for assessors and authorities in charge of the management of the environment and pollution.

Patterns of tobacco use among smokers prior to hospitalization for an acute cardiac event: Use of combusted and non-combusted products.

Use of tobacco products before or after a cardiac event increases risk of morbidity and mortality. Unlike cigarette smoking, which is generally screened in the healthcare system, identifying the use of other tobacco products remains virtually unexplored. This study aimed at characterizing the use of other non-combusted tobacco products in addition to combusted products among cardiac patients and identifying a profile of patients who are more likely to use non-combusted products. Patients (N = 168) hospitalized for a coronary event who reported being current cigarette smokers completed a survey querying sociodemographics, cardiac diagnoses, use of other tobacco products, and perceptions towards these products. Classification and regression tree (CART) analysis was used to identify which interrelationships of participants characteristics led to profiles of smoking cardiac patients more likely to also be using non-combusted tobacco products. Results showed that non-combusted tobacco product use ranged from 0% to 47% depending on patient characteristic combinations. Younger age and lower perception that cigarette smoking is responsible for their cardiac condition were the strongest predictive factors for use of non-combusted products. Tobacco product use among cardiac patients extends beyond combusted products (13.7% non-combusted product use), and consequently, screening in health care settings should be expanded to encompass other tobacco product use. This study also characterizes patients likely to be using non-combusted products in addition to combusted, a group at high-risk due to their multiple product use, but also a group that may be amenable to harm reduction approaches and evidence-based tobacco treatment strategies.

Lead exposure in common shelduck (Tadorna tadorna): Tracking the success of the Pb shot ban for hunting in Spanish wetlands.

Levels of lead (Pb) were analyzed in tissues of 25 Common shelduck (Tadorna tadorna) from La Albufera Natural Park (NP) in Valencia (Eastern Spain), which were found dead due to a botulism outbreak. The objective was to assess Pb exposure in waterfowl, fourteen years after the implementation of the Real Decreto 581/2001, which banned the use of Pb ammunition for hunting activities in internationally relevant wetlands. For this purpose, this study measured the actual ingestion of lead pellets in Common shelduck from La Albufera de Valencia and provide data on Pb residue concentrations in different tissues of this species breeding in this NP. The Pb distribution pattern in tissues was bone > kidney > liver > brain > muscle, with Pb concentrations of 778.96 ±â€¯998.64, 122.40 ±â€¯89.18, 92.08 ±â€¯57.65, 18.90 ±â€¯16.30 and 15.13 ±â€¯11.85 ng/g (wet weight), respectively. This work presents, as far as we are aware, the first published data on Pb concentrations in Common shelduck. The Pb levels detected were lower than those reported in other studies on Anatid species from Spanish wetlands, which may be explained by this ban. Moreover, lead concentrations found were below those levels for which any observable effect has been described for acute or chronic lead exposure.

Modeling nicotine regulation: A review of studies in smokers with mental health conditions.

Smokers with mental health conditions (MHCs) lose approximately 15 years of life relative to non-smokers without MHCs, of which two-thirds are attributable to smoking. The Food and Drug Administration (FDA) recently announced a new regulatory strategy for tobacco that includes a reduction in the nicotine content of cigarettes sold in the US to a minimally-addictive level. This action could improve cessation rates in smokers with MHCs by reducing their dependence on nicotine. However, nicotine reduction also could have unintended negative consequences in smokers with MHCs. Thus, it is important to conduct randomized controlled trials to investigate the potential effects of nicotine reduction in smokers with MHCs. Several studies of the acute or extended effects of nicotine reduction in smokers with emotional disorders or serious mental illness have been recently completed or are underway. Studies to date indicate that when smokers with MHCs are switched, under randomized, double-blind conditions, to cigarettes with very low nicotine content, they reduce their cigarette intake, with minimal or no effects on withdrawal, psychiatric symptoms, or compensatory smoking. However, some deleterious effects of nicotine reduction on cognitive performance measures in smokers with schizophrenia have been observed, which are offset by providing concurrent nicotine replacement. We review these studies and provide suggestions for potentially increasing the effectiveness of a nicotine reduction strategy for reducing smoking in people with MHCs. The research described was conducted in the United States in 2010-2018.

Tobacco use in cardiac patients: Perceptions, use, and changes after a recent myocardial infarction among US adults in the PATH study (2013-2015).

Smoking status following cardiac events strongly predicts future morbidity and mortality. Using a nationally representative sample of United States adults, aims of this study were (1) to estimate use of, and attitudes towards, tobacco products as a function of level of cardiac risk, and (2) to explore changes in attitudes and tobacco use among adults experiencing a recent myocardial infarction (MI). Data were obtained from the first and second waves of the Population Assessment of Tobacco and Health (PATH) study. Use and attitudes towards tobacco products were examined at Wave 1 among adults with no chronic health condition (n = 18,026), those with risk factors for heart disease (n = 4593), and those who reported ever having had an MI (n = 643). Changes in perceived risk of tobacco and use between the two waves and having an MI in the last 12 months (n = 240) were also examined. Those who reported lifetime MI were more likely to believe that smoking/using tobacco was causing/worsening a health problem. Having had a recent MI event increased perceived tobacco-related risk and attempts at reduction/quitting, but did not significantly impact combusted tobacco cessation/reduction or uptake of non-combusted tobacco products. Sociodemographic characteristics and use of other tobacco products were associated with change in use of tobacco products. Those who have an MI are sensitized to the harm of continued smoking. Nonetheless, having an MI does not predict quitting combusted tobacco use or switching to potentially reduced harm products. Intense intervention is necessary to reduce combusted use in this high-risk population.

Role of syncope in predicting adverse outcomes in patients with suspected Brugada syndrome undergoing standardized flecainide testing.

Aims: Sensitivity to flecainide testing results in suboptimal findings in patients with Brugada syndrome (BrS), leading to safety concerns. Because cardiac syncope effectively predicts outcomes in BrS, we aimed to explore its predictive value in a large cohort of negative and positive responders (NR and PR) to standard flecainide testing. Methods and results: We analysed the data of 251 consecutive patients, 177 NR vs. 74 PR, to flecainide testing, performed according to standard recommendations. Cardiac syncope was defined as syncope presenting without prodromal symptoms and in the absence of any specific situation. Comparing PR with NR, there were no differences regarding age (39 ± 15 vs. 44 ± 13 years; P = 0.052), male gender (70.1% vs. 66.2%; P = 0.553), and family history of sudden cardiac death in relatives younger than 45 years (27% vs. 27%; P = 1). Cardiac syncope was more frequent in PR (12.2% vs. 4%; P = 0.022), and previous sudden cardiac arrest (SCA) was documented only in PR (5.4% vs. 0%; P = 0.007). During the follow-up period (6.2 ± 3.3 years), one NR, who had previously experienced cardiac syncope, developed SCA 3 months after flecainide testing. Following resuscitation, a type I electrocardiogram was spontaneously recorded. The follow-up event rate was higher in patients with cardiac syncope, both in PR and in NR (P < 0.001 both). In a multivariate analysis, cardiac syncope was the unique variable that predicted adverse outcomes (hazard ratio 14.9, 95% confidence interval 1.84-121.25; P = 0.011). Conclusions: In patients with false-negative responses to the provocative testing with flecainide, cardiac syncope predicts SCA, allowing a more extensive and individualized evaluation.

Delta of the local ventriculo-atrial intervals at the septal location to differentiate tachycardia using septal accessory pathways from atypical atrioventricular nodal re-entry.

Aims: Tachycardia mediated by septal accessory pathways (AP) and atypical atrioventricular nodal re-entry (AVNRT) require careful electrophysiologic evaluation for differential diagnosis. We aim to describe the differential behaviour of local ventriculo-atrial (VA) intervals which predicts the tachycardia mechanism. Methods and results: The local VA intervals at the para-Hisian septum were measured under three different situations: (i) tachycardia; (ii) sustained entrainment from the right ventricular apex (RVA); and (iii) continuous pacing from the RVA during sinus rhythm. Differences were computed as follows: Δ-VAentr = VA during entrainment - VA during tachycardia; and Δ-VApac = VA while pacing during sinus rhythm - VA during tachycardia. In contrast to AVNRT, we hypothesized that an invariable retrograde conduction through the septal AP will keep the result of the subtractions close to 0 ms in cases of ortodromic atrioventricular re-entrant tachycardia (AVRT). We analysed 55 atypical AVNRT (45% posterior type) and 82 AVRT (10 anteroseptal, 18 para-Hisian, 12 mid-septal, and 42 posteroseptal). Δ-VAentr was longer for AVNRT (98.5 ± 40.3 ms) compared with septal AP (-5.7 ± 19.3 ms; P < 0.001). A value of 50 ms showed 98.7% sensitivity and 92% specificity (AUC 0.99; 95% CI 0.98-1). According to physiological criteria, a negative Δ-VAentr remains unobserved in the case of AVNRT (positive predictive value 100% for septal AP). Δ-VApac was also longer for AVNRT (66.5 ± 14.6 ms) compared with septal AP (-9.7 ± 3.3 ms; P < 0.001). A value of 50 ms showed 100% sensitivity and 74% specificity (AUC 0.86; 95% CI 0.76-0.93). Conclusions: Delta of the local VA intervals enables distinction between atypical AVNRT and AVRT mediated by septal AP.

E-cigarette awareness, perceived harmfulness, and ever use among U.S. adults.

The overarching aims of this study are to (a) estimate and update knowledge on rates and predictors of awareness, perceived harmfulness, and ever use of e-cigarettes among U.S. adults and (b) to utilize that information to identify risk-factor profiles associated with ever use. Data were collected from the 2015 Health Information National Trends Survey (N=3738). Logistic regression was used to explore relationships between sociodemographics (gender, age, race/ethnicity, sexual orientation, educational attainment, income, and census region), current use of other tobacco products (conventional cigarettes, cigars, and smokeless tobacco), ever use of alternative products (hookah, pipes, roll-your-own cigarettes, and snus) and e-cigarette awareness, perceived harm, and ever use. Classification and regression tree (CART) modeling was used to examine risk-factor profiles of e-cigarette ever use. Results showed that most respondents were aware of e-cigarettes (83.6%) and perceived them to be not at all or moderately harmful (54.7%). Prevalence of e-cigarette ever use was 22.4%. Current cigarette smoking and ever use of alternative tobacco products were powerful predictors of use. Other predictors of use of e-cigarettes were age, race/ethnicity, and educational attainment. Awareness and perceived harm were significant predictors among particular smoker subgroups. Fifteen risk profiles were identified across which prevalence of e-cigarette use varied from 6 to 94%. These results underscore the need to continue monitoring patterns of e-cigarette use. They also provide new knowledge regarding risk-profiles associated with striking differences in prevalence of e-cigarette use that have the potential to be helpful when considering the need for or impact of e-cigarette regulatory policies.