"I Thought Cancer was a Tobacco Issue": Perspectives of Veterans with and without HIV on Cancer and Other Health Risks Associated with Alcohol and Tobacco/Nicotine Use.

U.S. Veterans and people living with HIV (PWH) experience higher rates of unhealthy alcohol and tobacco/nicotine use than non-Veterans and people without HIV (PWoH). Both groups are susceptible to adverse health outcomes associated with alcohol and tobacco/nicotine use. We explored awareness of alcohol- and tobacco/nicotine-related cancer and immune health risks among Veterans Health Administration (VA) patients with and without HIV. Among a sample of 41 (46% PWH; 73% male; 39% Black) purposively-selected VA patients receiving care 2020-2021 we conducted semi-structured interviews via telephone; interviews were recorded, transcribed and analyzed using a Rapid Assessment Process. Purposive selection was based on HIV status, alcohol and/or tobacco/nicotine use, and demographics. Among participants, 66% reported current smoking, and most screened positive for unhealthy alcohol use. Participants had high awareness of cancer and other health risks related to smoking but low awareness of synergistic risks and cancer risks associated with alcohol use despite awareness of a range of other alcohol-related risks. Awareness of alcohol and/or tobacco/nicotine's impacts on the immune system was variable. Findings did not distinctly differ between PWH and PWoH. Low awareness of alcohol-related cancer risk, risks of co-occurring use, and varying awareness of the impacts of alcohol and tobacco/nicotine on the immune system suggest a need for improved messaging regarding substance use-related cancer and immune risk. This may be especially important among PWH, for whom the prevalence and adverse effects of alcohol and tobacco use, and immune dysfunction are higher.

Behavioral Activation mHealth Application for Smoking Cessation: A Randomized Controlled Pilot Trial.

BACKGROUND: Behavioral activation (BA) is an effective intervention for both depression and substance use disorders. Combining BA with a standard smoking cessation intervention may improve quit rates by addressing depressive symptoms, a key barrier to quitting. This study preliminarily evaluated the acceptability and efficacy of the BA-based Actify! mobile health application (mHealth app) for smoking cessation. METHODS: We conducted a pilot randomized controlled trial (n=242) comparing Actify! with the National Cancer Institute's (NCI) app for smoking cessation (QuitGuide) on acceptability (user satisfaction, app openings), smoking abstinence, and mechanisms of change (behavioral activation and depressive symptoms) at 8 weeks and 6 months post-randomization. Participants were US adults recruited online who smoked daily. RESULTS: Treatment satisfaction was uniformly higher in the Actify! arm. Number of app openings was similar across arms (M=34.3 openings over 8 weeks in both arms). Self-reported 30-day point prevalence abstinence (PPA) at 8 weeks was 12.6% for Actify! vs. 7.3% for QuitGuide. Differences in 30-day PPA continued through 6 months (18.5% for Actify! vs. 12.2% for QuitGuide). Changes between baseline and 8 weeks in depressive symptoms and behavioral activation favored Actify!. Planned subgroup analyses suggested greater benefit of Actify! among participants with pre-treatment mild to moderate depression symptom severity compared to those with no depression symptoms. CONCLUSIONS: Actify! showed considerable promise as a novel mHealth treatment, as evidenced by high usage and higher user satisfaction and quit rates than QuitGuide at both short- and long-term follow-up. The next step is to evaluate Actify! in a fully-powered efficacy trial. IMPLICATIONS: Study findings demonstrate the promise of a behavioral activation (BA)-based mobile health app (Actify!) for smoking cessation as a population-level intervention that can effectively address depressive symptoms as a risk factor for worse smoking treatment outcomes. The Actify! app is the first standalone BA-based app to demonstrate potential for improved acceptability and efficacy relative to a standard care comparison app, with user satisfaction and smoking quit rates descriptively exceeding those of the National Cancer Institute's QuitGuide app.

Acceptability and Adherence to Home, Kiosk, and Clinic Blood Pressure Measurement Compared to 24-H Ambulatory Monitoring.

BACKGROUND: The US Preventive Services Task Force recommends measuring blood pressure (BP) outside of clinic/office settings. While various options are available, including home devices, BP kiosks, and 24-h ambulatory BP monitoring (ABPM), understanding patient acceptability and adherence is a critical factor for implementation. OBJECTIVE: To compare the acceptability and adherence of clinic, home, kiosk, and ABPM measurement. DESIGN: Comparative diagnostic accuracy study which randomized adults to one of three BP measurement arms: clinic, home, and kiosk. ABPM was conducted on all participants. PARTICIPANTS: Adults (18-85 years) receiving care at 12 Kaiser Permanente Washington primary care clinics (Washington State, USA) with a high BP (≥ 138 mmHg systolic or ≥ 88 mmHg diastolic) in the electronic health record with no hypertension diagnosis and on no hypertensive medications and with high BP at a research screening visit. MEASURES: Patient acceptability was measured using a validated survey which was used to calculate an overall acceptability score (range 1-7) at baseline, after completing their assigned BP measurement intervention, and after completing ABPM. Adherence was defined based on the pre-specified number of BP measurements completed. KEY RESULTS: Five hundred ten participants were randomized (mean age 59 years), with mean BP of 150/88. Overall acceptability score was highest (i.e. most acceptable) for Home BP (mean 6.2, SD 0.7) and lowest (least acceptable) for ABPM (mean 5.0, SD 1.0); scores were intermediate for Clinic (5.5, SD 1.1) and Kiosk (5.4, SD 1.0). Adherence was higher for Home (154/170, 90.6%) and Clinic (150/172, 87.2%) than for Kiosk (114/168, 67.9%)). The majority of participants (467/510, 91.6%) were adherent to ABPM. CONCLUSIONS: Participants found home BP measurement most acceptable followed by clinic, BP kiosks, and ABPM. Our findings, coupled with recent evidence regarding the accuracy of home BP measurement, further support the routine use of home-based BP measurement in primary care practice in the US. TRIAL REGISTRATION: ClinicalTrials.gov NCT03130257 https://clinicaltrials.gov/ct2/show/NCT03130257.

Clinic, Home, and Kiosk Blood Pressure Measurements for Diagnosing Hypertension: a Randomized Diagnostic Study.

BACKGROUND: The US Preventive Services Task Force recommends blood pressure (BP) measurements using 24-h ambulatory monitoring (ABPM) or home BP monitoring before making a new hypertension diagnosis. OBJECTIVE: Compare clinic-, home-, and kiosk-based BP measurement to ABPM for diagnosing hypertension. DESIGN, SETTING, AND PARTICIPANTS: Diagnostic study in 12 Washington State primary care centers, with participants aged 18-85 years without diagnosed hypertension or prescribed antihypertensive medications, with elevated BP in clinic. INTERVENTIONS: Randomization into one of three diagnostic regimens: (1) clinic (usual care follow-up BPs); (2) home (duplicate BPs twice daily for 5 days); or (3) kiosk (triplicate BPs on 3 days). All participants completed ABPM at 3 weeks. MAIN MEASURES: Primary outcome was difference between ABPM daytime and clinic, home, and kiosk mean systolic BP. Differences in diastolic BP, sensitivity, and specificity were secondary outcomes. KEY RESULTS: Five hundred ten participants (mean age 58.7 years, 80.2% white) with 434 (85.1%) included in primary analyses. Compared to daytime ABPM, adjusted mean differences in systolic BP were clinic (-4.7mmHg [95% confidence interval -7.3, -2.2]; P<.001); home (-0.1mmHg [-1.6, 1.5];P=.92); and kiosk (9.5mmHg [7.5, 11.6];P<.001). Differences for diastolic BP were clinic (-7.2mmHg [-8.8, -5.5]; P<.001); home (-0.4mmHg [-1.4, 0.7];P=.52); and kiosk (5.0mmHg [3.8, 6.2]; P<.001). Sensitivities for clinic, home, and kiosk compared to ABPM were 31.1% (95% confidence interval, 22.9, 40.6), 82.2% (73.8, 88.4), and 96.0% (90.0, 98.5), and specificities 79.5% (64.0, 89.4), 53.3% (38.9, 67.2), and 28.2% (16.4, 44.1), respectively. LIMITATIONS: Single health care organization and limited race/ethnicity representation. CONCLUSIONS: Compared to ABPM, mean BP was significantly lower for clinic, significantly higher for kiosk, and without significant differences for home. Clinic BP measurements had low sensitivity for detecting hypertension. Findings support utility of home BP monitoring for making a new diagnosis of hypertension. TRIAL REGISTRATION: ClinicalTrials.gov NCT03130257 https://clinicaltrials.gov/ct2/show/NCT03130257.

Truncation of IFT80 causes early embryonic loss in Holstein cattle associated with Holstein haplotype 2.

Recessive alleles represent genetic risk in populations that have undergone bottleneck events. We present a comprehensive framework for identification and validation of these genetic defects, including haplotype-based detection, variant selection from sequence data, and validation using knockout embryos. Holstein haplotype 2 (HH2), which causes embryonic death, was used to demonstrate the approach. Holstein haplotype 2 was identified using a deficiency-of-homozygotes approach and confirmed to negatively affect conception rate and stillbirths. Five carriers were present in a group of 183 sequenced Holstein bulls selected to maximize the coverage of unique haplotypes. Three variants concordant with haplotype calls were found in HH2: a high-priority frameshift mutation resulting, and 2 low-priority variants (1 synonymous variant, 1 premature stop codon). The frameshift in intraflagellar 80 (IFT80) was confirmed in a separate group of Holsteins from the 1000 Bull Genomes Project that shared no animals with the discovery set. IFT80-null embryos were generated by truncating the IFT80 transcript at exon 2 or 11 using a CRISPR-Cas9 system. Abattoir-derived oocytes were fertilized in vitro, and zygotes were injected at the one-cell stage either with a guide RNA and CAS9 mRNA complex (n = 100) or Cas9 mRNA (control, n = 100) before return to culture, and replicated 3 times. IFT80 is activated at the 8-cell stage, and IFT80-null embryos arrested at this stage of development, which is consistent with data from mouse hypomorphs and HH2 carrier-to-carrier matings. This frameshift in IFT80 on chromosome 1 at 107,172,615 bp (p.Leu381fs) disrupts WNT and hedgehog signaling, and is responsible for the death of homozygous embryos.

The United States National Cancer Institute's Coordinated Research Effort on Tobacco Use as a Major Cause of Morbidity and Mortality among People with HIV.

The use of antiretroviral therapy for people with HIV (PWH) has improved life expectancy. However, PWH now lose more life-years to tobacco use than to HIV infection. Unfortunately, PWH smoke at higher rates and have more difficulty maintaining abstinence than the general population, compounding their risk for chronic disease. In this Commentary, we describe a United States National Cancer Institute-led initiative to address the relative lack of research focused on developing, testing, and implementing smoking cessation interventions for PWH. This initiative supports seven clinical trials designed to systematically test and/or develop and test adaptations of evidence-based smoking cessation interventions for PWH (eg, combination of behavioral and pharmacological). We summarize each project, including setting/recruitment sites, inclusion/exclusion criteria, interventions being tested, and outcomes. This initiative provides critical opportunities for collaboration and data harmonization across projects. The knowledge gained will inform strategies to assist PWH to promote and maintain abstinence, and ensure that these efforts are adaptable and scalable, thereby addressing one of the major threats to the health of PWH. Reducing smoking behavior may be particularly important during the COVID-19 pandemic given that smokers who become infected with SARS-CoV-2 may be at risk for more severe disease. IMPLICATIONS: This Commentary describes a National Cancer Institute-led initiative to advance the science and practice of treating tobacco use among PWH, which is now responsible for more life years lost than HIV. We describe the scope of the problem, the objectives of the initiative, and a summary of the seven funded studies. Harmonization of data across projects will provide information related to treatment mediators and moderators that was not previously possible. Stakeholders interested in tobacco cessation, including researchers, clinicians and public health officials, should be aware of this initiative and the evidence-base it will generate to advance tobacco treatment among this high-risk population.

A Reference Genome Assembly of American Bison, Bison bison bison.

Bison are an icon of the American West and an ecologically, commercially, and culturally important species. Despite numbering in the hundreds of thousands today, conservation concerns remain for the species, including the impact on genetic diversity of a severe bottleneck around the turn of the 20th century and genetic introgression from domestic cattle. Genetic diversity and admixture are best evaluated at genome-wide scale, for which a high-quality reference is necessary. Here, we use trio binning of long reads from a bison-Simmental cattle (Bos taurus taurus) male F1 hybrid to sequence and assemble the genome of the American plains bison (Bison bison bison). The male haplotype genome is chromosome-scale, with a total length of 2.65 Gb across 775 scaffolds (839 contigs) and a scaffold N50 of 87.8 Mb. Our bison genome is ~13× more contiguous overall and ~3400× more contiguous at the contig level than the current bison reference genome. The bison genome sequence presented here (ARS-UCSC_bison1.0) will enable new research into the evolutionary history of this iconic megafauna species and provide a new tool for the management of bison populations in federal and commercial herds.

A Reference Genome Assembly of Simmental Cattle, Bos taurus taurus.

Genomics research has relied principally on the establishment and curation of a reference genome for the species. However, it is increasingly recognized that a single reference genome cannot fully describe the extent of genetic variation within many widely distributed species. Pangenome representations are based on high-quality genome assemblies of multiple individuals and intended to represent the broadest possible diversity within a species. A Bovine Pangenome Consortium (BPC) has recently been established to begin assembling genomes from more than 600 recognized breeds of cattle, together with other related species to provide information on ancestral alleles and haplotypes. Previously reported de novo genome assemblies for Angus, Brahman, Hereford, and Highland breeds of cattle are part of the initial BPC effort. The present report describes a complete single haplotype assembly at chromosome-scale for a fullblood Simmental cow from an F1 bison-cattle hybrid fetus by trio binning. Simmental cattle, also known as Fleckvieh due to their red and white spots, originated in central Europe in the 1830s as a triple-purpose breed selected for draught, meat, and dairy production. There are over 50 million Simmental cattle in the world, known today for their fast growth and beef yields. This assembly (ARS_Simm1.0) is similar in length to the other bovine assemblies at 2.86 Gb, with a scaffold N50 of 102 Mb (max scaffold 156.8 Mb) and meets or exceeds the continuity of the best Bos taurus reference assemblies to date.

Tobacco quitline engagement and outcomes among primary care patients reporting use of tobacco or dual tobacco and cannabis: An observational study.

Background: Dual use of tobacco and cannabis is increasingly common, but it is unclear how it impacts individuals' interest in or ability to stop smoking. If dual users fail to engage in treatment or have worse treatment outcomes, it would suggest that tobacco treatment programs may need to be tailored to the specific needs of those using cannabis and tobacco. Methods: We conducted an observational study using electronic treatment records from adults (18 years and older) who (a) were enrolled in a regional healthcare system in Washington state, (b) sought tobacco cessation treatment through an insurance-covered quitline from July 2016 to December 2018 and (c) had cannabis use frequency during the period of their quitline enrollment documented in their electronic health record (EHR) (n = 1,390). Treatment engagement was defined by the total number of quitline counseling calls and web-logins completed. Point prevalent self-reported tobacco abstinence was assessed 6 months post-quitline enrollment. Results: Thirty-two percent of participants (n = 441) reported dual use of tobacco and any cannabis during the observation period; 9.4% (n = 130) reported daily cannabis use. Among dual users reporting daily cannabis use, 13.9% had a diagnosed cannabis user disorder in the EHR. Neither engagement with quitline counseling nor long-term tobacco abstinence rates differed between those using tobacco-only and either dual-use group (i.e., persons using any cannabis or daily cannabis). Conclusions: Dual use of tobacco and cannabis is common among smokers seen in primary care and those enrolling in quitline care, but it may not undermine tobacco quitline engagement or smoking cessation. Opportunities exist in the US to leverage quitlines to identify and intervene with dual users of tobacco and cannabis.HIGHLIGHTSTobacco quitline care was equally engaging and effective among tobacco users and dual users of tobacco and cannabisMany daily cannabis users calling tobacco quitlines likely have a cannabis use disorderTobacco quitlines can be leveraged to identify and intervene with dual users of tobacco and cannabis.

Validating the Use of Bovine Buccal Sampling as a Proxy for the Rumen Microbiota by Using a Time Course and Random Forest Classification Approach.

Analysis of the cow microbiome, as well as host genetic influences on the establishment and colonization of the rumen microbiota, is critical for development of strategies to manipulate ruminal function toward more efficient and environmentally friendly milk production. To this end, the development and validation of noninvasive methods to sample the rumen microbiota at a large scale are required. In this study, we further optimized the analysis of buccal swab samples as a proxy for direct bacterial samples of the rumen of dairy cows. To identify an optimal time for sampling, we collected buccal swab and rumen samples at six different time points relative to animal feeding. We then evaluated several biases in these samples using a machine learning classifier (random forest) to select taxa that discriminate between buccal swab and rumen samples. Differences in the inverse Simpson's diversity, Shannon's evenness, and Bray-Curtis dissimilarities between methods were significantly less apparent when sampling was performed prior to morning feeding (P < 0.05), suggesting that this time point was optimal for representative sampling. In addition, the random forest classifier was able to accurately identify nonrumen taxa, including 10 oral and putative feed-associated taxa. Two highly prevalent (>60%) taxa in buccal and rumen samples had significant variance in relative abundances between sampling methods but could be qualitatively assessed via regular buccal swab sampling. This work not only provides new insights into the oral community of ruminants but also further validates and refines buccal swabbing as a method to assess the rumen bacterial in large herds.IMPORTANCE The gastrointestinal tracts of ruminants harbor a diverse microbial community that coevolved symbiotically with the host, influencing its nutrition, health, and performance. While the influence of environmental factors on rumen microbes is well documented, the process by which host genetics influences the establishment and colonization of the rumen microbiota still needs to be elucidated. This knowledge gap is due largely to our inability to easily sample the rumen microbiota. There are three common methods for rumen sampling but all of them present at least one disadvantage, including animal welfare, sample quality, labor, and scalability. The development and validation of noninvasive methods, such as buccal swabbing, for large-scale rumen sampling is needed to support studies that require large sample sizes to generate reliable results. The validation of buccal swabbing will also support the development of molecular tools for the early diagnosis of metabolic disorders associated with microbial changes in large herds.

Comparative Effectiveness of Group-Delivered Acceptance and Commitment Therapy versus Cognitive Behavioral Therapy for Smoking Cessation: A Randomized Controlled Trial.

INTRODUCTION: Preliminary trial data suggest group-delivered acceptance and commitment therapy (ACT) might be effective for smoking cessation. If so, this could offer a viable alternative to mainstream behavioral therapies, such as those grounded in cognitive behavioral therapy (CBT). The goal of the current study was to compare the effectiveness of group-delivered ACT versus group-delivered CBT in a rigorous randomized trial design with long-term follow-up. METHODS: Participants (n = 450) were recruited from the Kaiser Permanente Washington health care system and randomized to either ACT-based group counseling or an attention-matched CBT-based group program. All were prescribed an 8-week course of nicotine patches. The primary outcome was self-reported 30-day point prevalence abstinence at 12 months post-randomization assessed with missing values imputed as smoking. Sensitivity analyses using multiple imputation and complete cases were examined, as were biochemically confirmed and 6-month outcomes. RESULTS: Thirty-day point prevalence abstinence rates at the 12-month follow-up did not differ between study arms in the primary analysis (13.8% ACT vs. 18.1% CBT, adjusted odds ratio = 0.68 [95% CI = 0.35 to 1.27], p = .23) or the sensitivity analyses. CONCLUSIONS: Group-based ACT and CBT had similar long-term quit rates in this methodologically rigorous randomized trial. Group-based ACT is a reasonable alternative to group-based CBT for smoking cessation. IMPLICATIONS: This study compared the effectiveness of group-based ACT with group-based CBT for smoking cessation using a rigorous, large-scale, attention-matched, randomized trial with 1-year follow-up. One-year cessation rates did not differ between group-based ACT and CBT, suggesting ACT-based intervention is a reasonable alternative to CBT-based counseling for smoking cessation. The results add to the nascent but growing literature assessing ACT and other mindfulness-based treatments for smoking cessation.

Long-Term Smoking Cessation Outcomes for Sexual Minority Versus Nonminority Smokers in a Large Randomized Controlled Trial of Two Web-Based Interventions.

INTRODUCTION: Despite greater smoking prevalence among sexual minority (SM) individuals relative to non-SM individuals, minimal research has examined whether SM smokers have differential success at quitting, and no prior treatment studies have examined differences within SM subgroups. There is also limited knowledge of the psychosocial characteristics of treatment-seeking SM smokers, which could inform targeted treatments. To address these gaps, we compared treatment outcomes and baseline characteristics for SM and non-SM smokers and for bisexual versus lesbian or gay smokers in a large randomized controlled trial of two web-based cessation treatments. METHODS: Trial participants completed a survey to assess baseline characteristics, including self-identification as either SM (n = 253; lesbian or gay, n = 122; bisexual, n = 131) or non-SM (n = 2384). The primary cessation outcome was complete-case, self-reported 30-day abstinence at 12 months after randomization. RESULTS: Cessation outcomes did not differ significantly for SM versus non-SM smokers (24% vs. 25%, adjusted OR = 0.91, 95% CI = 0.65 to 1.28) or across SM subgroups (24% for bisexual vs. 23% for lesbian or gay, adjusted OR = 1.01, 95% CI = 0.51 to 2.00), and there were no interactions with treatment group assignment. At baseline, SM smokers differed from non-SM smokers on most demographics, were more likely to screen positive for all mental health conditions assessed, and had greater exposure to other smokers in the home. CONCLUSIONS: Substantial differences in baseline characteristics of SM versus non-SM smokers and bisexual versus lesbian or gay smokers did not translate into differential treatment outcomes. Nonetheless, SM smokers' willingness or ability to quit smoking could be enhanced by taking their unique psychosocial profile into account when designing targeted interventions. IMPLICATIONS: The findings of this study, which included the largest sample of SM smokers in a prospective intervention trial to date, support those of a small extant body of literature showing no differences in treatment-assisted cessation outcomes between SM and non-SM smokers. Regardless of their quit rates relative to non-SM smokers, SM smokers' willingness or ability to quit smoking could potentially be enhanced by taking their unique psychosocial profile into account in intervention design, including their younger age, lower socioeconomic status, greater likelihood of being racial or ethnic minorities, and greater prevalence of mental health symptoms.

Which Method of Assessing Depression and Anxiety Best Predicts Smoking Cessation: Screening Instruments or Self-Reported Conditions?

INTRODUCTION: Affective disorders and symptoms (ADS) are predictive of lower odds of quitting smoking. However, it is unknown which approach to assessing ADS best predicts cessation. This study compared a battery of ADS screening instruments with a single, self-report question on predicting cessation. Among those who self-reported ADS, we also examined if an additional question regarding whether participants believed the condition(s) might interfere with their ability to quit added predictive utility to the single-item question. METHODS: Participants (N = 2637) enrolled in a randomized controlled trial of web-based smoking treatments completed a battery of five ADS screening instruments and answered a single-item question about having ADS. Those with a positive self-report on the single-item question were also asked about their interference beliefs. The primary outcome was complete-case, self-reported 30-day point prevalence abstinence at 12 months. RESULTS: Both assessment approaches significantly predicted cessation. Screening positive for ≥ one ADS in the battery was associated with 23% lower odds of quitting than not screening positive for any (p = .023); those with a positive self-report on the single-item had 39% lower odds of quitting than self-reporting no mental health conditions (p < .001). Area under the receiver operating characteristic curve values for the two assessment approaches were similar (p = .136). Adding the interference belief question to the single-item assessment significantly increased the area under the receiver operating characteristic curve value (p = .042). CONCLUSIONS: The single-item question assessing ADS had as much predictive validity, and possibly more, than the battery of screening instruments for identifying participants at risk for failing to quit smoking. Adding a question about interference beliefs significantly increased the predictive utility of the single-item question. IMPLICATIONS: This is the first study to demonstrate that a single-item question assessing ADS has at least as much predictive validity, and possibly more, than a battery of validated screening instruments for identifying smokers at highest risk for cessation failure. This study also demonstrates adding a question about interference beliefs significantly adds to the predictive utility of a single, self-report question about mental health conditions. Findings from this study can be used to inform decisions regarding how to assess ADS in the context of tobacco treatment settings.

Reducing Sitting Time in Obese Older Adults: The I-STAND Randomized Controlled Trial.

BACKGROUND: The authors tested the efficacy of the "I-STAND" intervention for reducing sitting time, a novel and potentially health-promoting approach, in older adults with obesity. METHODS: The authors recruited 60 people (mean age = 68 ± 4.9 years, 68% female, 86% White; mean body mass index = 35.4). The participants were randomized to receive the I-STAND sitting reduction intervention (n = 29) or healthy living control group (n = 31) for 12 weeks. At baseline and at 12 weeks, the participants wore activPAL devices to assess sitting time (primary outcome). Secondary outcomes included fasting glucose, blood pressure, and weight. Linear regression models assessed between-group differences in the outcomes. RESULTS: The I-STAND participants significantly reduced their sitting time compared with the controls (-58 min per day; 95% confidence interval [-100.3, -15.6]; p = .007). There were no statistically significant changes in the secondary outcomes. CONCLUSION: I-STAND was efficacious in reducing sitting time, but not in changing health outcomes in older adults with obesity.

Analysis of a large dataset reveals haplotypes carrying putatively recessive lethal and semi-lethal alleles with pleiotropic effects on economically important traits in beef cattle.

BACKGROUND: In livestock, deleterious recessive alleles can result in reduced economic performance of homozygous individuals in multiple ways, e.g. early embryonic death, death soon after birth, or semi-lethality with incomplete penetrance causing reduced viability. While death is an easy phenotype to score, reduced viability is not as easy to identify. However, it can sometimes be observed as reduced conception rates, longer calving intervals, or lower survival for live born animals. METHODS: In this paper, we searched for haplotypes that carry putatively recessive lethal or semi-lethal alleles in 132,725 genotyped Irish beef cattle from five breeds: Aberdeen Angus, Charolais, Hereford, Limousin, and Simmental. We phased the genotypes in sliding windows along the genome and used five tests to identify haplotypes with absence of or reduced homozygosity. Then, we associated the identified haplotypes with 44,351 insemination records that indicated early embryonic death, and postnatal survival records. Finally, we assessed haplotype pleiotropy by estimating substitution effects on estimates of breeding value for 15 economically important traits in beef production. RESULTS: We found support for one haplotype that carries a putatively recessive lethal (chromosome 16 in Simmental) and two haplotypes that carry semi-lethal alleles (chromosome 14 in Aberdeen Angus and chromosome 19 in Charolais), with population frequencies of 8.8, 15.2, and 14.4%, respectively. These three haplotypes showed pleiotropic effects on economically important traits for beef production. Their allele substitution effects are €2.30, €3.42, and €1.47 for the terminal index and €1.03, - €3.11, and - €0.88 for the replacement index, where the standard deviations for the terminal index are €22.52, €18.65, and €22.70 and for the replacement index they are €31.35, €29.82, and €35.79. We identified ZFAT as the candidate gene for semi-lethality in Aberdeen Angus, several candidate genes for the lethal Simmental haplotype, and no candidate genes for the semi-lethal Charolais haplotype. CONCLUSIONS: We analysed genotype, reproduction, survival, and production data to detect haplotypes that carry putatively recessive lethal or semi-lethal alleles in Irish beef cattle and identified one lethal and two semi-lethal haplotypes, which have pleiotropic effects on economically important traits in beef production.

Comparing Treatment Acceptability and 12-Month Cessation Rates in Response to Web-Based Smoking Interventions Among Smokers Who Do and Do Not Screen Positive for Affective Disorders: Secondary Analysis.

BACKGROUND: Web-based cessation programs are now common for intervening with smokers. However, it remains unclear how acceptable or effective these interventions are among people with affective disorders and symptoms (ADS; eg, depression and anxiety). Research examining this is extremely limited, with mixed results on cessation rates. Additional large studies are needed to more fully understand whether Web-based interventions are similarly used and equally effective among people with and without affective disorder symptomology. If not, more targeted Web-based interventions may be required. OBJECTIVE: The goal of the research was to compare Web-based treatment acceptability (defined by satisfaction and use) and 12-month cessation outcomes between smokers with and without ADS. METHODS: Participants (N=2512) were adult smokers enrolled in a randomized, comparative effectiveness trial of two Web-based smoking interventions designed for the general population of smokers. At baseline, participants reported demographic and smoking characteristics and completed measures assessing ADS. Participants were then classified into subgroups based on their self-reported ADS-either into a no ADS group or into six nonmutually exclusive subgroups: depression, posttraumatic stress disorder (PTSD), panic disorder (PD), generalized anxiety disorder (GAD), social anxiety disorder (SAD), and more than one ADS. Surveys at 12 months postrandomization included subjective ratings of treatment acceptability and self-reported smoking cessation. Treatment use (ie, number of log-ins and total duration of exposure) was assessed via automated records. RESULTS: Relative to the no ADS group, all six ADS subgroups reported significantly greater satisfaction with their assigned Web treatment program, but they spent less time logged in than those with no ADS. For number of log-ins, a treatment arm by ADS group interaction was observed across all ADS subgroups except GAD, suggesting that relative to the no ADS group, they logged in less to one website but not the other. At the 12-month follow-up, abstinence rates in the no ADS group (153/520, 29.42%) were significantly higher than for participants who screened positive for depression (306/1267, 24.15%; P=.03), PTSD (294/1215, 24.19%; P=.03), PD (229/1003, 23.83%; P=.009), and two or more ADS (323/1332, 24.25%; P=.03). Post hoc analyses suggest the lower quit rates may be associated with differences in baseline nicotine dependence and levels of commitment to resist smoking in difficult situations. Website use did not explain the differential abstinence rates. CONCLUSIONS: Despite reporting higher levels of treatment satisfaction, most smokers with ADS used their assigned intervention less often and had lower quit rates than smokers with no ADS at treatment onset. The results support the need for developing more targeted interventions for smokers with ADS. TRIAL REGISTRATION: Clinical Trials.gov NCT01812278; https://clinicaltrials.gov/ct2/show/NCT01812278 (Archived by WebCite at http://www.webcitation.org/78L9cNdG4).

Oral Health Promotion and Smoking Cessation Program Delivered via Tobacco Quitlines: The Oral Health 4 Life Trial.

OBJECTIVES: To assess the effects of a novel oral health promotion program (Oral Health 4 Life; OH4L) delivered through state-funded tobacco quitlines. METHODS: Using a semipragmatic design to balance experimental control and generalizability, we randomized US quitline callers (n = 718) to standard care or standard care plus OH4L. We followed participants for 6 months to assess effects on professional dental care and smoking abstinence. We collected data between 2015 and 2017. RESULTS: Participants were racially diverse (42% non-White) and socioeconomically disadvantaged. Most (71%) reported fair or poor oral health, and all were overdue for routine dental care. At 6 months, professional dental care and abstinence did not significantly differ between arms, but abstinence favored the experimental arm and was significantly higher among experimental participants at 2 months in a complete case sensitivity analysis. CONCLUSIONS: OH4L was not effective for promoting dental care, but integrating oral health counseling with quitline counseling may offer some advantage for smoking cessation. Public Health Implications. We offer a model for conducting semipragmatic trials and partnering with tobacco quitlines to evaluate population-level public health interventions.

Evaluation of a population-level strategy to promote tobacco treatment use among insured smokers: a pragmatic, randomized trial.

BACKGROUND: Most smokers do not use evidence-based smoking cessation treatment. Increasing utilization of these services is an important public health goal. Health care systems and insurers are well positioned to support this goal within their patient populations. We tested whether a brief, mail-based intervention increased utilization of tobacco cessation services among insured smokers. METHODS: Adult smokers were identified via automated health plan data and randomized to one of five treatment arms (n = 4767). Randomization was stratified by gender, age, and type of health plan coverage. Three arms received a letter containing motivational content and treatment referral information. Motivational content emphasized either the financial, health, or values-based benefits of quitting. One arm received a referral letter with no motivational content, and one arm received no letter. Enrollment in the referred tobacco cessation program was monitored for 5 months. Treatment was available to all participants through their insurance. RESULTS: Across all four letter conditions, 0.8% of participants enrolled in tobacco treatment compared to 0.9% in the no letter reference group (p = .69). No single letter condition was superior to the others (p = .71), but treatment uptake was greater among participants who received their care and coverage from the health plan versus those with insurance coverage only (1.2% vs. 0.3%, p < .01). CONCLUSIONS: A one-time, mailed letter is not a cost-effective strategy for promoting use of covered smoking cessation treatment within large health plan populations, particularly when the message source is an insurance provider only and does not also provide clinical care. Health plans and insurers should consider alternative outreach efforts to promote treatment uptake among smokers. TRIAL REGISTRATIONS: TRN registered retrospectively with ISRCTN registry ( www.isrctn.com ). Registered on 11/01/2018. Registration number: ISRCTN32311137 .

Acceptability of a sitting reduction intervention for older adults with obesity.

BACKGROUND: Older adults spend more time sitting than any other age group, contributing to poor health outcomes. Effective behavioral interventions are needed to encourage less sitting among older adults, specifically those with obesity, but these programs must be acceptable to the target population. We explored participant acceptance of a theory-based and technology-enhanced sitting reduction intervention designed for older adults (I-STAND). METHODS: The 12-week I-STAND intervention consisted of 6 health coaching contacts, a study workbook, a Jawbone UP band to remind participants to take breaks from sitting, and feedback on sitting behaviors (generated from wearing an activPAL device for 7 days at the beginning and mid-point of the study). Semi-structured interviews were conducted with 22 participants after they completed the intervention. Interview transcripts were iteratively coded by a team, and thematic analysis was used to identify and refine emerging themes. RESULTS: Overall, participants were satisfied with the I-STAND intervention, thought the sedentary behavior goals of the intervention were easy to incorporate, and found the technologies to be helpful additions to (but not substitutes for) health coaching. Barriers to standing more included poor health, ingrained sedentary habits, lack of motivation to change sedentary behavior, and social norms that dictate when it is appropriate to sit/stand. Facilitators to standing more included increased awareness of sitting, a sense of accountability, daily activities that involved standing, social support, and changing ways of interacting in the home environment. Participants reported that the intervention improved physical health, increased energy, increased readiness to engage in physical activity, improved mood, and reduced stress. CONCLUSIONS: The technology-enhanced sedentary behavior reduction intervention was acceptable, easy to incorporate, and had a positive perceived health impact on older adults with obesity. TRIAL REGISTRATION: The I-STAND study was registered at clinicaltrials.gov (ID: NCT02692560 ) February 2016.

Participant Recruitment and Retention in Remote eHealth Intervention Trials: Methods and Lessons Learned From a Large Randomized Controlled Trial of Two Web-Based Smoking Interventions.

BACKGROUND: Despite having many advantages, online eHealth trials are not without challenges-notably, participant recruitment, and outcome data retention. Moreover, publications from these trials rarely provide detailed information on the methods used for recruitment and retention or discuss implications of the methods for future studies. OBJECTIVE: To address this need for empirical guidance regarding recruitment and outcome data retention planning, we aim to describe the methods and lessons learned from the recruitment and retention procedures used in a large randomized trial of 2 Web-based smoking cessation interventions. METHODS: To ensure a demographically and geographically diverse participant sample, we used the recruitment strategies (1) traditional, (2) Web-based, and (3) online survey panel methods and adaptively modified each in response to recruitment success. At baseline, participants indicated how they heard about the study and answered demographic questions. To maximize trial retention at each of the 3-, 6-, and 12-month assessment points, 4 survey modalities (first Web, followed by phone, mail, and postcard) were sequentially timed over a 30-day period. Participants received US $25 for submitting their responses, regardless of modality, and received an additional US $10 bonus for completing the Web survey within 24h of electronic notification. RESULTS: We randomized 2637 smokers in 16 months and achieved 88% retention at 12-months. Participants (79.26% female, 72.60% Caucasian) were recruited from all 50 states. The majority of participants were recruited through Facebook (49.43%), followed by the survey panel (20.85%), free internet sources (14.54%), traditional media (11.34%), and Google ads (3.84%). Descriptively, participant demographics varied by recruitment source. Of the completed follow-up surveys, most were completed by Web (92%). Retention rates did not vary by recruitment source. CONCLUSIONS: Continuous monitoring and refinement of multiple recruitment methods, particularly of online advertising campaigns, allowed us to maximize the effectiveness of recruitment strategies in recruiting a large, diverse sample of smokers. Likewise, offering multiple follow-up survey modalities in sequential order along with time-dependent bonus incentives enabled us to obtain outcome data from a very high level of enrolled participants for the duration of the trial protocol. These strategies may be similarly useful in other trials. TRIAL REGISTRATION: ClinicalTrials.gov NCT01812278; https://clinicaltrials.gov/ct2/show/NCT01812278 (Archived by WebCite at http://www.webcitation.org/71gy5GLvO).