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Heart shape captures variation in cardiac structure beyond traditional phenotypes of mass and volume. Although observational studies have demonstrated associations with cardiometabolic risk factors and diseases, its genetic basis is less understood. We utilised cardiovascular magnetic resonance images from 45,683 UK Biobank participants to construct a heart shape atlas from bi-ventricular end-diastolic surface mesh models through principal component (PC) analysis. Genome-wide association studies were performed on the first 11 PCs that captured 83.6% of shape variance. We identified 43 significant loci, 14 were previously unreported for cardiac traits. Genetically predicted PCs were associated with cardiometabolic diseases. In particular two PCs (2 and 3) linked with more spherical ventricles being associated with increased risk of atrial fibrillation. Our study explores the genetic basis of multidimensional bi-ventricular heart shape using PCA, reporting new loci and biology, as well as polygenic risk scores for exploring genetic relationships of heart shape with cardiometabolic diseases., Competing Interests: Competing interests Dr Barriales-Villa has received consultant/advisor fees from MyoKardia/Bristol Myers Squibb, Cytokinetics, Sanofi, Pfizer, Amicus and Alnaylam. The remaining authors declare no competing interests., (© 2024. The Author(s).)

Background: Rapid and flexible data collection efforts are necessary for effective monitoring and research on tobacco and nicotine product use in a constantly evolving marketplace. The Rutgers Omnibus Survey (1) provides timely data on awareness and use of new and emerging tobacco products among adults in a rapid manner, (2) provides a platform for measurement experiments to help develop and refine measures of tobacco use that reflect the current marketplace, and (3) generates pilot data for grant applications and scientific manuscripts., Objective: This study aims to document the first 2 years of the Rutgers Omnibus Study through the reporting of methodology, fielding summaries, and sample characteristics., Methods: Launched in February 2022 and fielded quarterly thereafter, we survey convenience samples of 2000 to 3000 US adults aged 18-45 years recruited from Amazon Mechanical Turk (MTurk) using the MTurk Toolkit by CloudResearch. The questionnaire includes core and rotating modules and is designed to take approximately 10 minutes to complete through Qualtrics. The fielding duration is approximately 10 days per wave. Each wave includes both unique and repeating participants, and responses can be linked across waves by an anonymous ID., Results: Sample sizes ranged from 2082 (wave 8, December 2023) to 2989 (wave 1, February 2022), and the 8-wave longitudinal dataset included 10,334 participants, of whom 2477 had 3 or more data points. The cost per complete at each wave was low, ranging from US $2.46 to US $3.27 across waves. Key demographics were consistent across waves and similar to that of the general population, while tobacco product trial and past-30-day use were generally higher., Conclusions: The Rutgers Omnibus Study is a quarterly survey that is effective for rapidly assessing the use of emerging tobacco and nicotine products and can also be leveraged to conduct survey experiments, generate pilot data, and address both cross-sectional and longitudinal research questions., International Registered Report Identifier (irrid): RR1-10.2196/58203., (©Michelle T Bover Manderski, William J Young, Ollie Ganz, Cristine D Delnevo. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 16.10.2024.)

An elevated resting heart rate (RHR) is associated with increased cardiovascular mortality. Genome-wide association studies (GWAS) have identified > 350 loci. Uniquely, in this study we applied genetic fine-mapping leveraging tissue specific chromatin segmentation and colocalization analyses to identify causal variants and candidate effector genes for RHR. We used RHR GWAS summary statistics from 388,237 individuals of European ancestry from UK Biobank and performed fine mapping using publicly available genomic annotation datasets. High-confidence causal variants (accounting for > 75% posterior probability) were identified, and we collated candidate effector genes using a multi-omics approach that combined evidence from colocalisation with molecular quantitative trait loci (QTLs), and long-range chromatin interaction analyses. Finally, we performed druggability analyses to investigate drug repurposing opportunities. The fine mapping pipeline indicated 442 distinct RHR signals. For 90 signals, a single variant was identified as a high-confidence causal variant, of which 22 were annotated as missense. In trait-relevant tissues, 39 signals colocalised with cis-expression QTLs (eQTLs), 3 with cis-protein QTLs (pQTLs), and 75 had promoter interactions via Hi-C. In total, 262 candidate genes were highlighted (79% had promoter interactions, 15% had a colocalised eQTL, 8% had a missense variant and 1% had a colocalised pQTL), and, for the first time, enrichment in nervous system pathways. Druggability analyses highlighted ACHE, CALCRL, MYT1 and TDP1 as potential targets. Our genetic fine-mapping pipeline prioritised 262 candidate genes for RHR that warrant further investigation in functional studies, and we provide potential therapeutic targets to reduce RHR and cardiovascular mortality., (© 2024. The Author(s).)

Background: Ventricular repolarization time (ECG QT and JT intervals) is associated with malignant arrhythmia. Genome-wide association studies have identified 230 independent loci for QT and JT; however, 50% of their heritability remains unexplained. Previous work supports a causal effect of lower serum calcium concentrations on longer ventricular repolarization time. We hypothesized calcium interactions with QT and JT variant associations could explain a proportion of the missing heritability., Methods and Results: We performed genome-wide calcium interaction analyses for QT and JT intervals. Participants were stratified by their calcium level relative to the study distribution (top or bottom 20%). We performed a 2-stage analysis (genome-wide discovery [N=62 532] and replication [N=59 861] of lead variants) and a single-stage genome-wide meta-analysis (N=122 393, [European ancestry N=117 581, African ancestry N=4812]). We also calculated 2-degrees of freedom joint main and interaction and 1-degree of freedom interaction P values. In 2-stage and single-stage analyses, 50 and 98 independent loci, respectively, were associated with either QT or JT intervals (2-degrees of freedom joint main and interaction P value <5×10 -8 ). No lead variant had a significant interaction result after correcting for multiple testing and sensitivity analyses provided similar findings. Two loci in the single-stage meta-analysis were not reported previously ( SPPL2B and RFX6 )., Conclusions: We have found limited support for an interaction effect of serum calcium on QT and JT variant associations despite sample sizes with suitable power to detect relevant effects. Therefore, such effects are unlikely to explain a meaningful proportion of the heritability of QT and JT, and factors including rare variation and other environmental interactions need to be considered.

Introduction: Widespread misperceptions about nicotine may have unintended effects on public health. We examined associations between existing messages about nicotine or tobacco and beliefs about nicotine and reduced nicotine cigarettes (RNC)., Methods: 2962 U.S. 18-45-year-olds were randomized in a May 2022 web-based survey to view one of 26 text-based messages about tobacco or nicotine from three sources: ongoing research (n = 8), messages authorized by FDA for VLN cigarettes (n = 6), and FDA's "From Plant to Product to Puff" campaign (n = 12); six messages from FDA's campaign did not reference nicotine and were treated as the reference source. Analyses examined associations between messages, grouped by source and individually, with beliefs about nicotine and RNC addictiveness and harms., Results: Relative to FDA messages that did not reference nicotine, all message sources were associated with greater odds of a correct belief about nicotine (Odds Ratios [ORs] = 1.40-1.87, p's < 0.01); VLN messages were associated with greater correct beliefs about RNC addictiveness (b = 0.23, p < .05). No campaign produced greater correct beliefs about RNC harms. At the individual level, only five messages were associated with a correct belief about nicotine (ORs = 2.12-2.56, p-values < .01), and one with correct beliefs about RNC harms (b = 1.09, p < .05), vs. the reference message., Conclusions: Few existing messages improved understanding of the risks of nicotine separately from the risks of combustible products. Communication research is needed to promote greater public understanding of nicotine while minimizing unintended effects on nicotine and tobacco use., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: We assessed adults' perceived relative harm and addictiveness of products using FDA-authorized modified risk tobacco products (MRTP) claims and associations with intentions to use MRTPs., Methods: Data were from the May 2022 Rutgers Omnibus study among US 18-45-year-old adults (n=2964), collected by the Rutgers Institute for Nicotine and Tobacco Studies (INTS). Outcomes were perceived relative harm and addictiveness versus a typical cigarette and intentions to use a product stating a reduced harm claim (General Snus) or a reduced exposure claim (VLN King). We conducted regression analyses of associations between perceived relative harm and addictiveness and intentions to use each product, stratified by smoking status., Results: The minority of participants perceived products with a reduced harm claim as much less harmful vs. cigarettes (21 %, 19 %, 7 %, and 8 % among persons who smoked daily, smoked some days, formerly smoked, and never smoked respectively) and products with a reduced exposure claim as much less addictive vs. cigarettes (24 %, 26 %, 14 %, 20 % respectively). Perceived lower relative harm and addictiveness were significantly associated with higher intentions to use products stating reduced harm or reduced exposure claim across all smoking statuses with one exception (relative addictiveness was not associated with intention to use products stating the reduced harm claim among persons who formerly smoked)., Conclusions: Two current FDA-authorized MRTP claims were not effective in conveying that MRTPs were less harmful or addictive than cigarettes to most participants. Perceiving products as less harmful or addictive were significantly associated with intentions to use MRTPs., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024. Published by Elsevier B.V.)

Introduction: Accelerating smoking cessation, particularly among young adults, is a national priority for decreasing tobacco-related disease. Healthcare providers play a critical role in delivering tobacco treatment interventions to this population. This study examined associations of demographic and tobacco use characteristics with young adults' self-reported past-year clinical encounters to identify opportunities to facilitate cessation., Methods: We conducted cross-sectional, secondary analyses on a sample of 831 young adults aged 18-34 participating in the first wave of the National Young Adult Health Survey (NYAHS 2018-2019). Demographic and tobacco use characteristics were participants' sex, age, race, current cigarette use, and current other tobacco use. Clinical encounter outcomes were past-year self-report of (1) seeing a clinician, (2) being asked about tobacco use, and among those currently smoking, (3) being advised to quit smoking., Results: After adjustment for covariates, women (vs. men) had 2.16 times greater odds of reporting seeing a clinician, while Non-White (vs. White) young adults and those currently (vs. never) smoking had 69% and 47% lower odds. Women and those currently smoking had 2.98 and 2.66 times greater odds, respectively, of being asked about tobacco use. Among those who currently smoked, being not confident (vs. confident) about quitting smoking was associated with 69% lower odds of being advised to quit; those who reported moderate (vs. low) nicotine dependence had 3.11 times higher odds of being advised to quit., Conclusions: Sex, racial, and smoking status differences in young adults' clinical encounter outcomes suggest multiple opportunities for future smoking prevention and cessation intervention efforts., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Genetic testing in the inherited arrhythmia clinic informs risk stratification, clinical management, and family screening. Periodic review of variant classification is recommended as supporting evidence accrues over time. However, there is limited reporting of real-world data on the frequency and impact of variant reclassification., Objective: The purpose of this study was to determine the burden of variant reclassification in our inherited arrhythmia clinic and the impact on clinical management., Methods: Genetic testing reports for patients referred to our clinic from 2004-2020 were reviewed. Reported variants were reinvestigated using ClinVar, VarSome, and a literature review. Classification was updated using the American College of Medical Genetics and Genomics (ACMG) criteria and tested for association with arrhythmic events and modification of medical management., Results: We identified 517 patients (median age 37 years) who underwent gene panel testing. A variant of uncertain significance (VUS) was reported for 94 patients (18.2%) and more commonly identified when using large gene panels (P <.001). A total of 28 of 87 unique VUSs (32.2%) were reclassified to pathogenic/likely pathogenic (n = 11) or benign/likely benign (n = 17). Of 138 originally reported pathogenic variants, 7 (5.1%) lacked support using ACMG criteria. Variant reclassification was not associated with arrhythmic events; however, it did impact genotype-specific counseling and future therapeutic options., Conclusion: In our large real-world patient cohort, we identify a clinically important proportion of both pathogenic variants and VUSs with evidence for reclassification. These findings highlight the need for informed pretest counseling, a regular structured review of variants reported in genetic testing, and the potential benefits to patients for supporting genotype-guided therapy., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Hypertension affects more than one billion people worldwide. Here we identify 113 novel loci, reporting a total of 2,103 independent genetic signals (P < 5 × 10 -8 ) from the largest single-stage blood pressure (BP) genome-wide association study to date (n = 1,028,980 European individuals). These associations explain more than 60% of single nucleotide polymorphism-based BP heritability. Comparing top versus bottom deciles of polygenic risk scores (PRSs) reveals clinically meaningful differences in BP (16.9 mmHg systolic BP, 95% CI, 15.5-18.2 mmHg, P = 2.22 × 10 -126 ) and more than a sevenfold higher odds of hypertension risk (odds ratio, 7.33; 95% CI, 5.54-9.70; P = 4.13 × 10 -44 ) in an independent dataset. Adding PRS into hypertension-prediction models increased the area under the receiver operating characteristic curve (AUROC) from 0.791 (95% CI, 0.781-0.801) to 0.826 (95% CI, 0.817-0.836, ∆AUROC, 0.035, P = 1.98 × 10 -34 ). We compare the 2,103 loci results in non-European ancestries and show significant PRS associations in a large African-American sample. Secondary analyses implicate 500 genes previously unreported for BP. Our study highlights the role of increasingly large genomic studies for precision health research., (© 2024. The Author(s).)

Objective: Relighting, i.e., extinguishing, saving, and later relighting and smoking unfinished cigarettes, appears prevalent, may be associated with nicotine dependence and negative health outcomes, yet is poorly understood. We estimate the prevalence, frequency, correlates of, and reasons for, cigarette relighting., Methods: Survey respondents (n=676) were 18-45-year-old US-based Amazon Mechanical Turk (MTurk) participants who smoked cigarettes every/some days. Items assessed frequency of and reasons for relighting. Reported smoking sessions per day were compared to calculations based on reported cigarettes per day (CPD) and relighting frequency., Results: Seventy-two percent of those who smoked reported relighting cigarettes. Reasons included not having time to finish (77%), not feeling like finishing (75%), saving money or avoiding wasting (70%), and making cigarettes last longer (59%). Nearly half (44%) relight to cut down and 34% to reduce harm. Hispanic (OR=1.73, CI:1.03-2.91) and non-Hispanic Black respondents (OR= 2.23, CI:1.20-4.10) had higher odds of relighting than others, as did those who smoke within 30minutes of waking (OR=2.45, CI:1.33-4.52) or wake up at night to smoke (OR=2.40, CI:1.68-3.44) (all ps <0.05). Respondents demonstrated low consistency in reporting the number of times they smoke (first-lit and relit) compared to calculations based on CPD and relighting frequency., Conclusions: Relighting is associated with race, ethnicity, nicotine dependence, and is often done to save money, cut down smoking, and reduce harm. Among those who relight, "smoking session" frequency seemed to be underestimated. Single item smoking frequency measures may not be ideal for individuals who smoke and relight., Competing Interests: Declaration of Competing Interest There are no conflicts of interest by any author., (Copyright © 2024. Published by Elsevier B.V.)

Background: Shorter regimens for drug-resistant tuberculosis (DR-TB) have non-inferior efficacy compared with longer regimens, but QT prolongation is a concern. T-wave morphology abnormalities may be a predictor of QT prolongation., Research Design and Methods: STREAM Stage 1 was a randomized controlled trial in rifampicin-resistant TB, comparing short and long regimens. All participants had regular ECGs. QT/QTcF prolongation (≥500 ms or increase in ≥60 ms from baseline) was more common on the short regimen which contained high-dose moxifloxacin and clofazimine. Blinded ECGs were selected from the baseline, early (weeks 1-4), and late (weeks 12-36) time points. T-wave morphology was categorized as normal or abnormal (notched, asymmetric, flat-wave, flat peak, or broad). Differences between groups were assessed using Chi-Square tests (paired/unpaired, as appropriate)., Results: Two-hundred participants with available ECGs at relevant times were analyzed (QT prolongation group n  = 82; non-prolongation group n  = 118). At baseline, 23% (45/200) of participants displayed abnormal T-waves, increasing to 45% (90/200, p  < 0.001) at the late time point. Abnormalities were more common in participants allocated the Short regimen (75/117, 64%) than the Long (14/38, 36.8%, p  = 0.003); these occurred prior to QT/QTcF ≥500 ms in 53% of the participants (Long 2/5; Short 14/25)., Conclusions: T-wave abnormalities may help identify patients at risk of QT prolongation on DR-TB treatment., Trial Registration: The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT02409290). Current Controlled Trial number, ISRCTN78372190.

Adult and paediatric patients with pathogenic variants in the gene encoding succinate dehydrogenase (SDH) subunit B (SDHB) often have locally aggressive, recurrent or metastatic phaeochromocytomas and paragangliomas (PPGLs). Furthermore, SDHB PPGLs have the highest rates of disease-specific morbidity and mortality compared with other hereditary PPGLs. PPGLs with SDHB pathogenic variants are often less differentiated and do not produce substantial amounts of catecholamines (in some patients, they produce only dopamine) compared with other hereditary subtypes, which enables these tumours to grow subclinically for a long time. In addition, SDHB pathogenic variants support tumour growth through high levels of the oncometabolite succinate and other mechanisms related to cancer initiation and progression. As a result, pseudohypoxia and upregulation of genes related to the hypoxia signalling pathway occur, promoting the growth, migration, invasiveness and metastasis of cancer cells. These factors, along with a high rate of metastasis, support early surgical intervention and total resection of PPGLs, regardless of the tumour size. The treatment of metastases is challenging and relies on either local or systemic therapies, or sometimes both. This Consensus statement should help guide clinicians in the diagnosis and management of patients with SDHB PPGLs., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Young adults are generally hard to survey, presenting researchers with numerous difficulties. They are hard to locate and contact due to high mobility. They are hard to persuade and exhibit high levels of resistance to survey participation. As a result, they pose a greater challenge for longitudinal surveys. This paper explores the role of mode of data collection in young adults' decisions to stay in a longitudinal panel. We draw on data from the National Young Adult Health Survey (NYAHS). NYAHS is a longitudinal study (three annual waves and 2 brief between-wave follow-up surveys) of adults aged 18-34 initially recruited in 2019 through RDD sampling of cell phone numbers nationwide. All sampled cell phone numbers were randomly assigned to one of three experimental conditions; the conditions differed in mode of data collection used in subsequent interviews once screened in. In the first condition, young adults continue all rounds of interviews by telephone ("telephone only" condition). The second group of young adults completed one round of interview by web and the rest by telephone ("telephone mostly" condition). The last third was asked to complete three interviews online and two interviews by telephone ("web mostly" condition). We examined the impact of mode switching on young adults' likelihood of participating in later surveys and on nonresponse bias in key survey outcomes. We found that switching young adults from telephone to web had an immediate negative effect on their likelihood of participating in that web survey, but it did not have a continued negative effect. Switching them from web to telephone increased response rates and reduced nonresponse bias. The findings have important practical implications on how to survey young adults.

Heart rate variability (HRV) is a cardiac autonomic marker with predictive value in cardiac patients. Ultra-short HRV (usHRV) can be measured at scale using standard and wearable ECGs, but its association with cardiovascular events in the general population is undetermined. We aimed to validate usHRV measured using ≤ 15-s ECGs (using RMSSD, SDSD and PHF indices) and investigate its association with atrial fibrillation, major adverse cardiac events, stroke and mortality in individuals without cardiovascular disease. In the National Survey for Health and Development (n = 1337 participants), agreement between 15-s and 6-min HRV, assessed with correlation analysis and Bland-Altman plots, was very good for RMSSD and SDSD and good for PHF. In the UK Biobank (n = 51,628 participants, 64% male, median age 58), after a median follow-up of 11.5 (11.4-11.7) years, incidence of outcomes ranged between 1.7% and 4.3%. Non-linear Cox regression analysis showed that reduced usHRV from 15-, 10- and 5-s ECGs was associated with all outcomes. Individuals with low usHRV (< 20th percentile) had hazard ratios for outcomes between 1.16 and 1.29, p < 0.05, with respect to the reference group. In conclusion, usHRV from ≤ 15-s ECGs correlates with standard short-term HRV and predicts increased risk of cardiovascular events in a large population-representative cohort., (© 2023. The Author(s).)

Introduction: Lung cancer is the leading cause of cancer death in the U.S. Combusted tobacco use, the primary risk factor, accounts for 90% of all lung cancers. Early detection of lung cancer improves survival, yet lung cancer screening rates are much lower than those of other cancer screening tests. Electronic health record (EHR) systems are an underutilized tool that could improve screening rates., Methods: This study was conducted in the Rutgers Robert Wood Johnson Medical Group, a university-affiliated network in New Brunswick, NJ. Two novel EHR workflow prompts were implemented on July 1, 2018. These prompts included fields to determine tobacco use and lung cancer screening eligibility and facilitated low-dose computed tomography ordering for eligible patients. The prompts were designed to improve tobacco use data entry, allowing for better lung cancer screening eligibility identification. Data were analyzed in 2022 retrospectively for the period July 1, 2017 to June 30, 2019. The analyses represented 48,704 total patient visits., Results: The adjusted odds of patient record completeness to determine eligibility for low-dose computed tomography (AOR=1.19, 95% CI=1.15, 1.23), eligibility for low-dose computed tomography (AOR=1.59, 95% CI=1.38, 1.82), and whether low-dose computed tomography was ordered (AOR=1.04, 95% CI=1.01, 1.07) all significantly increased after the electronic medical record prompts were implemented., Conclusions: These findings show the utility and benefit of EHR prompts in primary care settings to increase identification for lung cancer screening eligibility as well as increased low-dose computed tomography ordering., (Copyright © 2023 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Genome-wide association studies of blood pressure (BP) have identified >1,000 loci, but the effector genes and biological pathways at these loci are mostly unknown. Using published association summary statistics, we conducted annotation-informed fine-mapping incorporating tissue-specific chromatin segmentation and colocalization to identify causal variants and candidate effector genes for systolic BP, diastolic BP, and pulse pressure. We observed 532 distinct signals associated with ≥2 BP traits and 84 with all three. For >20% of signals, a single variant accounted for >75% posterior probability, 65 were missense variants in known (SLC39A8, ADRB2, and DBH) and previously unreported BP candidate genes (NRIP1 and MMP14). In disease-relevant tissues, we colocalized >80 and >400 distinct signals for each BP trait with cis-eQTLs and regulatory regions from promoter capture Hi-C, respectively. Integrating mouse, human disorder, gene expression and tissue abundance data, and literature review, we provide consolidated evidence for 436 BP candidate genes for future functional validation and discover several potential drug targets., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023. Published by Elsevier Inc.)

Background: Premium cigar use is infrequent compared with the use of other tobacco products, including other cigar types (eg, cigarillos), though current measurement methods for premium cigar use have limitations. Accordingly, prevalence estimates from existing surveillance studies likely underestimate the true prevalence of premium cigar use., Aims and Methods: Using an online convenience sample of adults (ages 18-45 years) surveyed in February 2022, we examined premium or traditional cigar prevalence and characterized users based on four definitions of use: (1) past-year use, (2) past 30-day use, (3) use every day or some days, and (4) use every day, some days, or rarely, using a novel, one-item measure. We examined demographics, cigar use behaviors, and other tobacco product use for each definition and conducted sensitivity analyses using cigar brands., Results: Prevalence estimates ranged from 1.8% using Definition 3 to 11.6% using Definition 1. Regardless of definition, premium or traditional cigar users were largely male, white, and aged 25-45 years. A large proportion of users based on Definition 3 were aged 25-34 years, had a regular premium cigar brand, smoked cigars on more than one day in the past month, used cannabis in the past month, and reported perceiving premium cigars as less harmful compared with cigarettes., Discussion: Prevalence estimates of premium or traditional cigar use varied by more than fivefold based on the definition of use and user characteristics varied by definition. Existing national surveys are likely underestimating the prevalence and patterns of premium cigar use., Implications: Given that the negative health effects of premium cigars vary based on how the cigars are used (eg, frequency or duration), as well as co-use with other tobacco products and substances (eg, alcohol and cannabis), accurate measurement of these products is important for understanding patterns of use and their impact on public health., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco.)

Purpose: The prevalence of rapid eye movement obstructive sleep apnea (REM-OSA) varies among reports. It remains unclear whether or not patients with REM-OSA experience more severe daytime sleepiness and poorer sleep quality than those with sleep-stage-independent obstructive sleep apnea (IND-OSA). We investigated the prevalence of REM-OSA in a Korean population sample and determined whether or not REM-OSA was associated with poor sleep quality and daytime sleepiness., Method: In this retrospective study. we defined "REM-OSA 1" as an apnea-hypopnea index (AHI) ≥ 5 and AHI REM /AHI NREM ratio ≥ 2. Patients who also had an AHI NREM  < 15 were classified as "REM-OSA 2" and those with an AHI NREM  < 8 and REM sleep duration ≥ 10.5 min were classified as "REM-OSA 3." Patient characteristics, Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), and polysomnography variables were compared between the REM-OSA and IND-OSA groups., Results: Among 483 patients, the prevalence rates of REM-OSA 1-3 were 10.3%, 5.5%, and 2.2% respectively. OSA severity was significantly lower in REM-OSA 1-3 than in IND-OSA. The proportion of women was significantly higher in REM-OSA 1-3 than IND-OSA groups. Patients with REM-OSA 2 and 3 had a significantly lower body mass index than those with IND-OSA. Patients with moderate-to-severe REM-OSA had significantly higher PSQI scores than those with IND-OSA. The AHI REM was significantly correlated with the ESS and PSQI scores., Conclusions: Despite the relatively low prevalence and severity of REM-OSA, it may reduce sleep quality and increase daytime sleepiness in some patients., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The 3-dimensional spatial and 2-dimensional frontal QRS-T angles are measures derived from the vectorcardiogram. They are independent risk predictors for arrhythmia, but the underlying biology is unknown. Using multi-ancestry genome-wide association studies we identify 61 (58 previously unreported) loci for the spatial QRS-T angle (N = 118,780) and 11 for the frontal QRS-T angle (N = 159,715). Seven out of the 61 spatial QRS-T angle loci have not been reported for other electrocardiographic measures. Enrichments are observed in pathways related to cardiac and vascular development, muscle contraction, and hypertrophy. Pairwise genome-wide association studies with classical ECG traits identify shared genetic influences with PR interval and QRS duration. Phenome-wide scanning indicate associations with atrial fibrillation, atrioventricular block and arterial embolism and genetically determined QRS-T angle measures are associated with fascicular and bundle branch block (and also atrioventricular block for the frontal QRS-T angle). We identify potential biology involved in the QRS-T angle and their genetic relationships with cardiovascular traits and diseases, may inform future research and risk prediction., (© 2023. The Author(s).)

Aims: Wearable devices are transforming the electrocardiogram (ECG) into a ubiquitous medical test. This study assesses the association between premature ventricular and atrial contractions (PVCs and PACs) detected on wearable-format ECGs (15 s single lead) and cardiovascular outcomes in individuals without cardiovascular disease (CVD)., Methods and Results: Premature atrial contractions and PVCs were identified in 15 s single-lead ECGs from N = 54 016 UK Biobank participants (median age, interquartile range, age 58, 50-63 years, 54% female). Cox regression models adjusted for traditional risk factors were used to determine associations with atrial fibrillation (AF), heart failure (HF), myocardial infarction (MI), stroke, life-threatening ventricular arrhythmias (LTVAs), and mortality over a period of 11.5 (11.4-11.7) years. The strongest associations were found between PVCs (prevalence 2.2%) and HF (hazard ratio, HR, 95% confidence interval = 2.09, 1.58-2.78) and between PACs (prevalence 1.9%) and AF (HR = 2.52, 2.11-3.01), with shorter prematurity further increasing risk. Premature ventricular contractions and PACs were also associated with LTVA ( P < 0.05). Associations with MI, stroke, and mortality were significant only in unadjusted models. In a separate UK Biobank sub-study sample [UKB-2, N = 29,324, age 64, 58-60 years, 54% female, follow-up 3.5 (2.6-4.8) years] used for independent validation, after adjusting for risk factors, PACs were associated with AF (HR = 1.80, 1.12-2.89) and PVCs with HF (HR = 2.32, 1.28-4.22)., Conclusion: In middle-aged individuals without CVD, premature contractions identified in 15 s single-lead ECGs are strongly associated with an increased risk of AF and HF. These data warrant further investigation to assess the role of wearable ECGs for early cardiovascular risk stratification., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

This study explores the extent to which psychiatrists are familiar with, and utilize, the USPHS guidelines for treating tobacco use and dependence (i.e., the 5A's), deliver cessation treatment, and the barriers they perceive to doing so. An original, national survey of 141 psychiatrists revealed that most Ask patients if they smoke (81.6%). Fewer Advise them to stop (78.7%) and Assess their willingness to quit (73.6%). A minority Assist with a quit plan (15.9%) and Arrange for follow-up (26.4%). Just 11.9% have used the USPHS guidelines in clinical practice; 37% have never heard of them. Even among those who say they have used the USPHS guidelines, implementation of the 5A's is quite low. Time-related factors were the most common barriers to cessation delivery (51.4%). Patient factors (30%) and financial/resource factors (25%) were less common. There is a strong need for increased implementation of clinical guidelines for evidence-based tobacco treatments among psychiatrists., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Coronary artery disease (CAD) and major adverse cardiovascular events (MACE) are the leading causes of death in the general population, but risk stratification remains suboptimal. CAD genetic risk scores (GRSs) predict risk independently from clinical tools, like QRISK3. We assessed the added value of GRSs for a variety of cardiovascular traits (CV GRSs) for predicting CAD and MACE and tested their early-life screening potential by comparing against the CAD GRS only., Methods: We used data from 379 581 participants in the UK Biobank without known cardiovascular conditions (follow-up, 11.3 years; 3.3% CAD cases and 5.2% MACE cases). In a training subset (50%) we built 3 scores: QRISK3; QRISK3 and an established CAD GRS; and QRISK3, the CAD GRS and the CV GRSs. In an independent subset (50%), we evaluated each score's performance using the concordance index, odds ratio and net reclassification index. We then repeated the analyses without considering QRISK3., Results: For CAD, the combination of QRISK3 and the CAD GRS had a better performance than QRISK3 alone (concordance index, 0.766 versus 0.753; odds ratio, 5.47 versus 4.82; net reclassification index, 7.7%). Adding the CV GRSs did not significantly improve risk stratification. When only looking at genetic information, the combination of CV GRSs and the CAD GRS had a better performance than the CAD GRS alone (concordance index, 0.637 versus 0.625; odds ratio, 2.17 versus 2.07; net reclassification index, 3.3%). Similar results were obtained for MACE., Conclusions: In individuals without known cardiovascular disease, the inclusion of CV GRSs to a clinical tool and an established CAD GRS does not improve CAD or MACE risk stratification. However, their combination only with the CAD GRS increases prediction performance indicating potential use in early-life screening before the advanced development of conventional cardiovascular risk factors.

Introduction: We assessed the prevalence of non-type 1 Brugada pattern (T1BrP) in children and young adults from the Sudden Cardiac Death-Screening Of risk factorS cohort and the diagnostic yield of nonexpert manual and automatic algorithm electrocardiogram (ECG) measurements., Methods: Cross-sectional study. We reviewed 14 662 ECGs and identified 2226 with a rSr'-pattern in V1-V2. Among these, 115 were classified by experts in hereditary arrhythmic-syndromes as having or not non-T1BrP, and were compared with measurements of 5 ECG-derived parameters based on a triangle formed by r' -wave (d(A), d(B), d(B)/h, β-angle) and ST-ascent, assessed both automatically and manually by nonexperts. We estimated intra- and interobserver concordance for each criterion, calculated diagnostic accuracy and defined the most appropriate cut-off values., Results: A rSr'-pattern in V1-V2 was associated with higher PQ interval and QRS duration, male gender, and lower body mass index (BMI). The manual measurements of non-T1BrP criteria were moderately reproducible with high intraobserver and moderate interobserver concordance coefficients (ICC: 0.72-0.98, and 0.63-0.76). Criteria with higher discriminatory capacity were: distance d(B) (0.72; 95% confidence interval [CI]: 0.65-0.80) and ST-ascent (0.87; 95% CI: 0.82-0.92), which was superior to the 4 r'-wave criteria together (area under curve [AUC: 0.74]). We suggest new cut-offs with improved combination of sensitivity and specificity: d(B) ≥ 1.4 mm and ST-ascent ≥ 0.7 mm (sensitivity: 1%-82%; specificity: 71%-84%), that can be automatically measured to allow classification in four morphologies with increasing non-T1BrP probability., Conclusion: rSr'-pattern in precordial leads V1-V2 is a frequent finding and the detection of non-T1BrP by using the aforementioned five measurements is reproducible and accurate. In this study, we describe new cut-off values that may help untrained clinicians to identify young individuals who may require further work-up for a potential Brugada Syndrome diagnosis., (© 2022 Wiley Periodicals LLC.)

Introduction: Tobacco packaging elements have been shown to influence product perceptions and use intentions. Garcia y Vega's Game cigarillos are distinct from other brands in their use of "natural leaf" on packaging. The term "natural" has been linked to misperceptions about lower risk in the context of cigarettes. This study examines the impact of the "natural leaf" descriptor and pack color on young adults' cigarillo perceptions and intentions., Methods: In April-June 2020, we conducted an online experiment with 1,063 young adults (ages 18-34) that were past year users of cigars, vaping products, or marijuana. Subjects were randomly assigned to view one of eight images of Game cigarillo packs that varied in color and presence of the "natural leaf" descriptor., Results: Purple packaging increased perceptions that the product tasted good, smelled nice, was flavored, and that a typical user was young. "Natural leaf" increased beliefs that the product contained high quality tobacco and that a typical user was trendy. When on grey packs, it increased favorable perceptions compared to when on brightly colored packs, including perceptions that the product tasted good, was fresh, that a typical user was trendy, and that the product was flavored., Conclusions: This study is the first to present quantitative evidence on the impact of the "natural leaf" descriptor on cigarillo perceptions and intentions, extending work that has been done in the context of cigarettes. Utilizing highly realistic stimuli, findings demonstrate that both the term "natural leaf" and packaging color can increase favorable perceptions of cigarillos., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The QT interval is an electrocardiographic measure representing the sum of ventricular depolarization and repolarization, estimated by QRS duration and JT interval, respectively. QT interval abnormalities are associated with potentially fatal ventricular arrhythmia. Using genome-wide multi-ancestry analyses (>250,000 individuals) we identify 177, 156 and 121 independent loci for QT, JT and QRS, respectively, including a male-specific X-chromosome locus. Using gene-based rare-variant methods, we identify associations with Mendelian disease genes. Enrichments are observed in established pathways for QT and JT, and previously unreported genes indicated in insulin-receptor signalling and cardiac energy metabolism. In contrast for QRS, connective tissue components and processes for cell growth and extracellular matrix interactions are significantly enriched. We demonstrate polygenic risk score associations with atrial fibrillation, conduction disease and sudden cardiac death. Prioritization of druggable genes highlight potential therapeutic targets for arrhythmia. Together, these results substantially advance our understanding of the genetic architecture of ventricular depolarization and repolarization., (© 2022. The Author(s).)

The 2021 National Youth Tobacco Survey (NYTS) was completed by youth online during class time, either in school or at home due to the COVID-19 pandemic. Given the role of NYTS data in tobacco regulatory science, it is vital to understand the effect of survey settings (home, school) on tobacco-use estimates. We used a series of multivariable logistic regressions to examine whether survey settings (home vs. school) predicted current e-cigarette use among high school students, controlling for other known predictors of e-cigarette use as well as the pandemic learning model that was dominant in students' counties (e.g., nearly all at-home, majority in school). We observed a significant survey setting effect. Those who completed the survey in school had higher odds of current e-cigarette use than those who completed the same survey at home (AOR = 1.74); this effect was attenuated when we controlled for the pandemic learning model (AOR = 1.38). Moreover, e-cigarette use was independently associated with students' learning model; students whose schools were nearly entirely in-person had the highest odds of e-cigarette use compared to students whose learning model was nearly all at-home (AOR = 1.65). Survey setting is a methodological artifact in the 2021 NYTS. Perceived privacy and peer effects can potentially explain this artifact.

Many factors can shift cigarette brand preference, and surveillance is an important tactic to inform regulatory strategy. The objective of this study was to identify shifts in top brands' overall and menthol market share from 2014 to 2019. We used data from the National Survey on Drug Use and Health public use datasets, which are a nationally representative, cross-sectional survey of people aged 12+ in the USA. In our analysis of top brands, we accounted for consumption patterns and computed the percent change in market share for each brand. We observed that overall market share declined for nearly all brands, though top moderately priced brands gained share. Half of the top brands with menthol styles grew in menthol market share. We observed three primary shifts in the cigarette market: brands that gained the most menthol market share were brands with both menthol and non-menthol in their product lineups; menthol contributed substantially to discount brands' market share increases; the two premium brands that employed "natural" descriptors experienced increased market share. Research should continue to focus on trends that influence cigarette market share, as the cigarette market in the USA is likely to look very different in five years than it does today.

Since 2018, our research team has fielded national, probability surveys of internal medicine physicians. We expected our usually high response rates to fall in the 2021 iteration of the survey due to challenges related to the COVID-19 pandemic and our inability to offer all participants a $50 upfront incentive as we had previously. To understand the independent impacts of the lower incentive and surveying physicians in the context of the pandemic, we fielded an experiment varying the incentive amount physicians were offered. Our results suggest that while higher incentives still lead to higher response rates during COVID-19, the higher incentive did not achieve comparable pre-COVID response rates. We conclude with additional data on the impact of the incentives on survey cost, number of reminders needed, and the mode in which respondents chose to complete the survey.

Background: Young adults' early adoption of new cell phone technologies have created challenges to survey recruitment but offer opportunities to combine random digit dialing (RDD) sampling with web mode data collection. The National Young Adult Health Survey was designed to test the feasibility of this methodology., Objective: In this study, we compared response rates across the telephone mode and web mode, assessed sample representativeness, examined design effects (DEFFs), and compared cigarette smoking prevalence to a gold standard national survey., Methods: We conducted a survey experiment where the sampling frame was randomized to single-mode telephone interviews, telephone-to-web sequential mixed mode, and single-mode web survey. A total of 831 respondents aged 18 to 34 years were recruited via RDD at baseline. A soft launch was conducted prior to main launch. We compared the web mode to the telephone modes (ie, single-mode and mixed mode) at wave 1 based on the American Association for Public Opinion Research response rate 3 for screening and extended surveys. Base-weighted demographic distributions were compared to the American Community Survey. The sample was calibrated to the US Census Bureau's American Community Survey to calculate DEFFs and to compare cigarette smoking prevalence to the National Health Interview Survey. Prevalence estimates are estimated with sampling weights and are presented with unweighted sample sizes. Consistency of estimates was judged by 95% CI., Results: The American Association for Public Opinion Research response rate 3 was higher in the telephone mode than in the web mode (24% and 30% vs 6.1% and 12.5%, for soft launch and main launch, respectively), which was reflected in response rate 3 for screening and extended surveys. During the soft launch, the extended survey and eligibility rate were low for respondents pushed to the web mode. To boost productivity and survey completes for the web condition, the main launch used cell phone numbers from the sampling frame where the sample vendor matched the number to auxiliary data, which suggested that the number likely belonged to an adult in the target age range. This increased the eligibility rate, but the screener response rate was lower. Compared to population distribution from the US Census Bureau, the telephone mode overrepresented men (57.1% [unweighted n=412] vs 50.9%) and those enrolled in college (40.3% [unweighted n=269] vs 23.8%); it also underrepresented those with a Bachelor of Arts or Science (34.4% [unweighted n=239] vs 55%). The web mode overrepresented White, non-Latinos (70.7% [unweighted n=90] vs 54.4%) and those with some college education (30.4% [unweighted n=40] vs 7.6%); it also underrepresented Latinos (13.6% [unweighted n=20] vs 20.7%) and those with a high school or General Education Development diploma (15.3% [unweighted n=20] vs 29.3%). The DEFF measure was 1.28 (subpopulation range 0.96-1.93). The National Young Adult Health Survey cigarette smoking prevalence was consistent with the National Health Interview Survey overall (15%, CI 12.4%-18% [unweighted 149/831] vs 13.5%, CI 12.3%-14.7% [unweighted 823/5552]), with notable deviation among 18- to 24-year-olds (15.6%, CI 11.3%-22.2% [unweighted 51/337] vs 8.7%, CI 7.1%-10.6% [unweighted 167/1647]), and those with education levels lower than Bachelor of Arts or Science (24%, CI 19.3%-29.4% [unweighted 123/524] vs 17.1%, CI 15.6%-18.7% [unweighted 690/3493])., Conclusions: RDD sampling for a web survey is not feasible for young adults due to its low response rate. However, combining this methodology with RDD telephone surveys may have a great potential for including media and collecting autophotographic data in population surveys., (©Daniel Alexander Gundersen, Jonathan Wivagg, William J Young, Ting Yan, Cristine D Delnevo. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 20.12.2021.)

Background: Compared with heterosexuals, sexual minorities in the United States experience a higher incidence of negative physical and mental health outcomes. However, a variety of measurement challenges limit researchers' ability to conduct meaningful survey research to understand these disparities. Despite the prevalence of additional identities, many national health surveys only offer respondents 3 substantive options for reporting their sexual identities (straight/heterosexual, gay or lesbian, and bisexual), which could lead to measurement error via misreporting and item nonresponse., Objective: This study compared the traditional 3-option approach to measuring sexual identity with an expanded approach that offered respondents 5 additional options., Methods: An online survey experiment conducted among New Jersey residents between March and June 2021 randomly assigned 1254 young adults (ages 18-21) to answer either the 3-response measure of sexual identity or the expanded item. Response distributions for each measure were compared as were the odds of item nonresponse., Results: The expanded version of the question appeared to result in more accurate reporting among some subgroups and induced less item nonresponse; 12% (77/642) of respondents in the expanded version selected a response that was not available in the shorter version. Females answering the expanded item were less likely to identify as gay or lesbian (2.1% [10/467] vs. 6.6% [30/457]). Females and Non-Hispanic Whites were slightly more likely to skip the shorter version than the longer version (1.1% [5/457 for females and 3/264 for Non-Hispanic Whites] vs. 0% [0/467 for females and 0/277 for Non-Hispanic Whites]). About 5% (32/642) of respondents answering the longer item were unsure of their sexual identity (a similar option was not available in the shorter version). Compared with respondents answering the longer version of the question, those answering the shorter version had substantially greater odds of skipping the question altogether (odds ratio 9.57, 95% CI 1.21-75.74; P=.03)., Conclusions: Results favor the use of a longer, more detailed approach to measuring sexual identity in epidemiological research. Such a measure will likely allow researchers to produce more accurate estimates of health behaviors and outcomes among sexual minorities., (©William J Young, Michelle T Bover Manderski, Ollie Ganz, Cristine D Delnevo, Mary Hrywna. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 13.12.2021.)

The resting QT interval, an electrocardiographic (ECG) measure of ventricular myocardial repolarization, is a heritable risk marker of cardiovascular mortality, but the mechanisms remain incompletely understood. Previously reported candidate genes have provided insights into the regulatory mechanisms of the QT interval. However, there are still important knowledge gaps. We aimed to gain new insights by (i) providing new candidate genes, (ii) identifying pleiotropic associations with other cardiovascular traits, and (iii) scanning for sexually dimorphic genetic effects. We conducted a genome-wide association analysis for resting QT interval with ~9.8 million variants in 52 107 individuals of European ancestry without known cardiovascular disease from the UK Biobank. We identified 40 loci, 13 of which were novel, including 2 potential sex-specific loci, explaining ~11% of the trait variance. Candidate genes at novel loci were involved in myocardial structure and arrhythmogenic cardiomyopathy. Investigation of pleiotropic effects of QT interval variants using phenome-wide association analyses in 302 000 unrelated individuals from the UK Biobank and pairwise genome-wide comparisons with other ECG and cardiac imaging traits revealed genetic overlap with atrial electrical pathology. These findings provide novel insights into how abnormal myocardial repolarization and increased cardiovascular mortality may be linked., (© The Author(s) 2021. Published by Oxford University Press.)

We conducted a survey experiment among US physicians to evaluate whether question wording impacted perceptions about the health effects of nicotine. 926 physicians were randomized to receive one of two versions of a question matrix that asked about the "extent to which they agree or disagree that 'nicotine' (Version 1) or 'nicotine, on its own,' (Version 2) directly contributes to" birth defects, cardiovascular disease (CVD), cancer, depression, and chronic obstructive pulmonary disease (COPD). We evaluated whether question condition predicted strong agreement and/or agreement with each statement, and assessed demographic correlates of each outcome while adjusting for question version. Physicians who received Version 2 were less likely to "strongly agree" that nicotine directly caused birth defects (Prevalence Ratio (PR) 0.84, 95% CI 0.72-0.98), CVD (PR 0.89, 95% CI 0.84-0.95), cancer (PR 0.81, 95% CI 0.75-0.87), and COPD (PR 0.78, 95% CI 0.72-0.84). Females were more likely to "strongly agree" that nicotine directly contributes to birth defects and cancer, and family physicians were most likely to "strongly agree" that nicotine directly contributes to CVD, cancer, and COPD. Question wording is important when measuring physicians' beliefs about nicotine; however, even after accounting for question version, misperceptions about the direct health effects of nicotine were common and varied by sex and specialty.

The electrocardiogram (ECG) is a commonly used clinical tool that reflects cardiac excitability and disease. Many parameters are can be measured and with the improvement of methodology can now be quantified in an automated fashion, with accuracy and at scale. Furthermore, these measurements can be heritable and thus genome wide association studies inform the underpinning biological mechanisms. In this review we describe how we have used the resources in UK Biobank to undertake such work. In particular, we focus on a substudy uniquely describing the response to exercise performed at scale with accompanying genetic information., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Aim: The mortality of patients with infective endocarditis (IE) is high. The management of patients with large vegetations is controversial. This study sought to investigate the association of vegetation size on outcomes including valve destruction, embolism and mortality., Methods and Results: One hundred and forty-two (142) patients with definite IE and transoesophageal echocardiography (TEE) imaging available for analysis were identified and data retrospectively reviewed. Vegetation length, width and area were measured. Severe valve destruction was defined as the composite of one or more of severe valve regurgitation, abscess, pseudoaneurysm, perforation or fistula. Associations with 6-month mortality were identified by Cox regression analysis. Eighty (80) (56.3%) patients had evidence of valve destruction on TEE. Vegetation length ≥10 mm and vegetation area ≥50 mm 2 were significantly associated with increased risk of valve destruction, (both odds ratio OR 1.21, p=0.03 and p=0.02 respectively). Thirty-nine (39) (72.2%) patients who had an embolic event, did so prior initiation of antibiotics. Six (6)-month mortality was 18.3%. In the surgically managed group, vegetation size was not associated with mortality. In the medically managed group, vegetation area (mm 2 ) was associated with increased mortality (HR 1.01, p<0.01) along with age (HR 1.06, p=0.03)., Conclusion: Vegetation length ≥10 mm or area ≥50 mm 2 are associated with increased risk of valve destruction. Vegetation size may also predict mortality in medically managed but not surgically managed patients with IE. Further studies to evaluate whether surgery in patients with large vegetation size improves outcomes is warranted., (Copyright © 2020 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)