Managing tobacco use: the neglected cardiovascular disease risk factor

Cigarette smoking is a major risk factor for cardiovascular disease (CVD) and the leading avoidable cause of death worldwide. Exposure to secondhand smoke (SHS) increases the risk of CVD among non-smokers. Smoking cessation benefits all smokers, regardless of age or amount smoked. The excess risk of CVD is rapidly reversible, and stopping smoking after a myocardial infarction reduces an individual's risk of CVD mortality by 36% over 2 years. Smoking cessation is a key component of primary and secondary CVD prevention strategies, but tobacco use often receives less attention from cardiologists than other risk factors, despite the availability of proven treatments that improve smoking cessation rates. Both psychosocial counselling and pharmacotherapy are effective methods to help smokers quit, but they are most effective when used together. The first-line medications licensed to aid smoking cessation, nicotine replacement therapy, bupropion and varenicline, are effective in and appropriate for patients with CVD. An evidence-based approach for physicians is to routinely ask all patients about smoking status and SHS exposure, advise all smokers to quit and all patients to adopt smoke-free policies for their home and car, and offer all smokers in the office or hospital brief counselling, smoking cessation pharmacotherapy, and referral to local programmes where psychosocial support can be sustained in person or by telephone. Like other chronic diseases, tobacco use requires a long-term management strategy. It deserves to be managed as intensively as other CVD risk factor

Relationships of Cotinine and Self-Reported Cigarette Smoking With Hemoglobin A1cA_{1c} in the U.S.

OBJECTIVE: Whether nicotine leads to a persistent increase in blood glucose levels is not clear. Our objective was to assess the relationship between cotinine, a nicotine metabolite, and glycated hemoglobin (Hb$A_{1c}$), an index of recent glycemia. RESEARCH DESIGN AND METHODS: We used cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2008. We limited our analysis to 17,287 adults without diabetes. We created three cotinine categories: <0.05 ng/mL, 0.05–2.99 ng/mL, and ≥3 ng/mL. RESULTS: Using self-report, 25% of the sample were current smokers, 24% were former smokers, and 51% were nonsmokers. Smokers had a higher mean Hb$A_{1c}$ (5.36% ± 0.01 SE) compared with never smokers (5.31% ± 0.01) and former smokers (5.31% ± 0.01). In a similar manner, mean Hb$A_{1c}$ was higher among participants with cotinine ≥3 ng/mL (5.35% ± 0.01) and participants with cotinine 0.05–2.99 ng/mL (5.34% ± 0.01) compared with participants with cotinine <0.05 ng/mL (5.29% ± 0.01). In multivariable-adjusted analysis, we found that both a cotinine ≥3 ng/mL and self-reported smoking were associated with higher Hb$A_{1c}$ compared with a cotinine <0.05 ng/mL or not smoking. People with a cotinine level ≥3 ng/mL had a relative 5% increase in Hb$A_{1c}$ compared with people with a cotinine level <0.05 ng/mL, and smokers had a relative 7% increase in Hb$A_{1c}$ compared with never smokers. CONCLUSIONS: Our study suggests that cotinine is associated with increased Hb$A_{1c}$ in a representative sample of the U.S. population without diabetes

Motivational interviewing to reduce substance-related consequences: Effects for incarcerated adolescents with depressed mood

Background: The impact of depressed mood on Motivational Interviewing (MI) to reduce risky behaviors and consequences in incarcerated adolescents was examined in this brief report. Methods: Adolescents (N = 189) were randomly assigned to receive MI or Relaxation Training (RT). Results: At 3-month follow-up assessment, MI significantly reduced risks associated with marijuana use, with a trend towards reducing risks associated with alcohol use. There was also a trend for depressive symptoms to be associated with reduced risks after release. Interaction effects were non-significant, indicating no moderating effects for depressed mood on treatment outcome. Conclusions: MI may be a useful treatment for incarcerated adolescents in order to reduce risks and consequences associated with substance use after release

Motivation to change alcohol use and treatment engagement in incarcerated youth

Adolescents have been reported to be less motivated to engage and remain in substance abuse treatment than adults. When they appear motivated, it is often due to external motivators such as family pressure or court mandated treatment. The purpose of this study was to determine if adolescents\u27 motivation to change alcohol use was related to treatment engagement while incarcerated and alcohol use after release. Participants (N = 114) were youth in a state correctional facility in the Northeast and included adolescents who engaged in at least monthly drinking. Motivation to change alcohol use was measured by the Alcohol Ladder (AL), and treatment engagement was measured by the Treatment Participation Questionnaire (comprised of positive and negative treatment engagement). Measures were administered at baseline, 2 months in facility follow up, and 3 months post release follow up. Analysis indicated acceptable test-retest stability (r = .388, p ≤ .001). The AL at 3 months post release significantly predicted quantity and frequency of alcohol use after release. The AL at baseline also significantly predicted positive and negative treatment engagement at 2 months into incarceration (i.e., 2 months in facility follow up) indicating predictive validity. These results suggest that the AL is a reliable, valid, and useful instrument for incarcerated youth

Genetic variation in adaptive traits and seed transfer zones for Pseudoroegneria spicata (bluebunch wheatgrass) in the northwestern United States

A genecological approach was used to explore genetic variation in adaptive traits in Pseudoroegneria spicata, a key restoration grass, in the intermountain western United States. Common garden experiments were established at three contrasting sites with seedlings from two maternal parents from each of 114 populations along with five commercial releases commonly used in restoration. Traits associated with size, flowering phenology, and leaf width varied considerably among populations and were moderately correlated with the climates of the seed sources. Pseudoroegneria spicata populations from warm, arid source environments were smaller with earlier phenology and had relatively narrow leaves than those from mild climates with cool summers, warm winters, low seasonal temperature differentials, high precipitation, and low aridity. Later phenology was generally associated with populations from colder climates. Releases were larger and more fecund than most of the native ecotypes, but were similar to native populations near their source of origin. Differences among native populations associated with source climates that are logical for survival, growth, and reproduction indicate that genetic variation across the landscape is adaptive and should be considered during restoration. Results were used to delineate seed transfer zones and population movement guidelines to ensure adapted plant materials for restoration activities.Keywords: Pseudoroegneria spicata, Plant adaptation, Climate change, Seed zones, Genecology, Seed transfe

Variants in WFS1 and Other Mendelian Deafness Genes are Associated with Cisplatin-Associated Ototoxicity

Cisplatin is one of the most commonly used chemotherapy drugs worldwide and one of the most ototoxic. We sought to identify genetic variants that modulate cisplatin-associated ototoxicity (CAO). Experimental Design: We performed a genome-wide association study (GWAS) of CAO using quantitative audiometry (4-12 kHz) in 511 testicular cancer survivors of European genetic ancestry. We performed polygenic modeling and functional analyses using a variety of publicly available databases. We used an electronic health record cohort to replicate our top mechanistic finding. Results: One SNP, rs62283056, in the first intron of Mendelian deafness gene WFS1 (wolframin ER transmembrane glycoprotein) and an expression quantitative trait locus (eQTL) for WFS1 met genome-wide significance for association with CAO (P=1.4x10-8). A significant interaction between cumulative cisplatin dose and rs62283056 genotype was evident, indicating that higher cisplatin doses exacerbate hearing loss in patients with the minor allele (P=0.035). The association between decreased WFS1 expression and hearing loss was replicated in an independent BioVU cohort (n=18,620 patients, Bonferroni adjusted P\u3c0.05). Beyond this top signal, we show CAO is a polygenic trait and that SNPs in and near 84 known Mendelian deafness genes are significantly enriched for low P-values in the GWAS (P=0.048). Conclusions: We show for the first time the role of WFS1 in CAO and document a statistically significant interaction between increasing cumulative cisplatin dose and rs62283056 genotype. Our clinical translational results demonstrate that pre-therapy patient genotyping to minimize ototoxicity could be useful when deciding between cisplatin-based chemotherapy regimens of comparable efficacy with different cumulative doses

Expressions 1988

https://openspace.dmacc.edu/expressions/1031/thumbnail.jp

Acute pain pathways:protocol for a prospective cohort study

INTRODUCTION: Opioid analgesics are often used to treat moderate-to-severe acute non-cancer pain; however, there is little high-quality evidence to guide clinician prescribing. An essential element to developing evidence-based guidelines is a better understanding of pain management and pain control among individuals experiencing acute pain for various common diagnoses. METHODS AND ANALYSIS: This multicentre prospective observational study will recruit 1550 opioid-naïve participants with acute pain seen in diverse clinical settings including primary/urgent care, emergency departments and dental clinics. Participants will be followed for 6 months with the aid of a patient-centred health data aggregating platform that consolidates data from study questionnaires, electronic health record data on healthcare services received, prescription fill data from pharmacies, and activity and sleep data from a Fitbit activity tracker. Participants will be enrolled to represent diverse races and ethnicities and pain conditions, as well as geographical diversity. Data analysis will focus on assessing patients’ patterns of pain and opioid analgesic use, along with other pain treatments; associations between patient and condition characteristics and patient-centred outcomes including resolution of pain, satisfaction with care and long-term use of opioid analgesics; and descriptive analyses of patient management of leftover opioids. ETHICS AND DISSEMINATION: This study has received approval from IRBs at each site. Results will be made available to participants, funders, the research community and the public. TRIAL REGISTRATION NUMBER: NCT04509115

Exome sequencing in bipolar disorder identifies AKAP11 as a risk gene shared with schizophrenia

We report results from the Bipolar Exome (BipEx) collaboration analysis of whole-exome sequencing of 13,933 patients with bipolar disorder (BD) matched with 14,422 controls. We find an excess of ultra-rare protein-truncating variants (PTVs) in patients with BD among genes under strong evolutionary constraint in both major BD subtypes. We find enrichment of ultra-rare PTVs within genes implicated from a recent schizophrenia exome meta-analysis (SCHEMA; 24,248 cases and 97,322 controls) and among binding targets of CHD8. Genes implicated from genome-wide association studies (GWASs) of BD, however, are not significantly enriched for ultra-rare PTVs. Combining gene-level results with SCHEMA, AKAP11 emerges as a definitive risk gene (odds ratio (OR) = 7.06, P = 2.83 × 10-9). At the protein level, AKAP-11 interacts with GSK3B, the hypothesized target of lithium, a primary treatment for BD. Our results lend support to BD's polygenicity, demonstrating a role for rare coding variation as a significant risk factor in BD etiology