The value of biosamples in smoking cessation trials:a review of genetic, metabolomic, and epigenetic findings

Introduction: Human genetic research has succeeded in definitively identifying multiple genetic variants associated with risk for nicotine dependence and heavy smoking. To build on these advances, and to aid in reducing the prevalence of smoking and its consequent health harms, the next frontier is to identify genetic predictors of successful smoking cessation and also of the efficacy of smoking cessation treatments ("pharmacogenomics"). More broadly, additional biomarkers that can be quantified from biosamples also promise to aid "Precision Medicine" and the personalization of treatment, both pharmacological and behavioral. Aims and Methods: To motivate ongoing and future efforts, here we review several compelling genetic and biomarker findings related to smoking cessation and treatment. Results: These Key results involve genetic variants in the nicotinic receptor subunit gene CHRNA5, variants in the nicotine metabolism gene CYP2A6, and the nicotine metabolite ratio. We also summarize reports of epigenetic changes related to smoking behavior. Conclusions: The results to date demonstrate the value and utility of data generated from biosamples in clinical treatment trial settings. This article cross-references a companion paper in this issue that provides practical guidance on how to incorporate biosample collection into a planned clinical trial and discusses avenues for harmonizing data and fostering consortium-based, collaborative research on the pharmacogenomics of smoking cessation. Implications: Evidence is emerging that certain genotypes and biomarkers are associated with smoking cessation success and efficacy of smoking cessation treatments. We review key findings that open potential avenues for personalizing smoking cessation treatment according to an individual's genetic or metabolic profile. These results provide important incentive for smoking cessation researchers to collect biosamples and perform genotyping in research studies and clinical trials.</p

Transcranial electrical and magnetic stimulation (tES and TMS) for addiction medicine: A consensus paper on the present state of the science and the road ahead

There is growing interest in non-invasive brain stimulation (NIBS) as a novel treatment option for substance-use disorders (SUDs). Recent momentum stems from a foundation of preclinical neuroscience demonstrating links between neural circuits and drug consuming behavior, as well as recent FDA-approval of NIBS treatments for mental health disorders that share overlapping pathology with SUDs. As with any emerging field, enthusiasm must be tempered by reason; lessons learned from the past should be prudently applied to future therapies. Here, an international ensemble of experts provides an overview of the state of transcranial-electrical (tES) and transcranial-magnetic (TMS) stimulation applied in SUDs. This consensus paper provides a systematic literature review on published data – emphasizing the heterogeneity of methods and outcome measures while suggesting strategies to help bridge knowledge gaps. The goal of this effort is to provide the community with guidelines for best practices in tES/TMS SUD research. We hope this will accelerate the speed at which the community translates basic neuroscience into advanced neuromodulation tools for clinical practice in addiction medicine

Individualized treatment for tobacco dependence in addictions treatment settings: the role of current depressive symptoms on outcomes at 3 and 6 months

Introduction: Individuals with concurrent tobacco dependence and other addictions often report symptoms of low mood and depression and as such may have more difficulty quitting smoking. We hypothesized that current symptoms of depression would be a significant predictor of quit success among a group of smokers receiving individualized treatment for tobacco dependence within addiction treatment settings.Methods: Individuals in treatment for other addictions were enrolled in a smoking cessation program involving brief behavioral counseling and individualized dosing of nicotine replacement therapy. The baseline assessment included the Patient Health Questionnaire (PHQ9) for depression. Smoking cessation outcomes were measured at 3 and 6 months post-enrollment. Bivariate associations between cessation outcomes and PHQ9 score were analyzed.Results: Of the 1,196 subjects enrolled to date, 1,171 (98%) completed the PHQ9. Moderate to severe depression (score >9) was reported by 28% of the sample, and another 29% reported mild depression (score between 5 and 9). Contrary to the extant literature and other findings by our own group, there was no association between current depression and cessation outcome at either 3 months (n = 1,171) (17.0% in those with PHQ9 > 9 vs. 19.8% in those with PHQ9 < 5, p = .32) or 6 months (n = 834) (17.8% vs. 18.9%, p = .74).Conclusions: Contrary to our hypothesis, depression severity as measured by the PHQ9 did not predict cessation outcome in this clinical population. A possible explanation may be the individualized treatment and supportive environment of an addictions treatment setting. These data indicate that patients in an addictions treatment setting can successfully quit smoking regardless of current depressive symptoms

Variability in patient sociodemographics, clinical characteristics, and healthcare service utilization among 107,302 treatment seeking smokers in Ontario: A cross-sectional comparison.

BackgroundSince 2005, the Smoking Treatment for Ontario Patients (STOP) program has provided smoking cessation treatment of varying form and intensity to smokers through 11 distinct treatment models, either in-person at partnering healthcare organizations or remotely via web or telephone. We aimed to characterize the patient populations reached by different treatment models.MethodsWe linked self-report data to health administrative databases to describe sociodemographics, physical and mental health comorbidity, healthcare utilization and costs. Our sample consisted of 107,302 patients who enrolled between 18Oct2005 and 31Mar2016, across 11 models operational during different time periods.ResultsPatient populations varied on sociodemographics, comorbidity burden, and healthcare usage. Enrollees in the Web-based model were youngest (median age: 39; IQR: 29-49), and enrollees in primary care-based Family Health Teams were oldest (median: 51; IQR: 40-60). Chronic Obstructive Pulmonary Disease and hypertension were the most common physical health comorbidities, twice as prevalent in Family Health Teams (32.3% and 30.8%) than in the direct-to-smoker (Web and Telephone) and Pharmacy models (13.5%-16.7% and 14.7%-17.7%). Depression, the most prevalent mental health diagnosis, was twice as prevalent in the Addiction Agency (52.1%) versus the Telephone model (25.3%). Median healthcare costs in the two years up to enrollment ranged from $1,787 in the Telephone model to$9,393 in the Addiction Agency model.DiscussionWhile practitioner-mediated models in specialized and primary care settings reached smokers with more complex healthcare needs, alternative settings appear better suited to reach younger smokers before such comorbidities develop. Although Web and Telephone models were expected to have fewer barriers to access, they reached a lower proportion of patients in rural areas and of lower socioeconomic status. Findings suggest that in addition to population-based strategies, embedding smoking cessation treatment into existing healthcare settings that reach patient populations with varying disparities may enhance equitable access to treatment

A method for co-creation of an evidence-based patient workbook to address alcohol use when quitting smoking in primary care: a case study

Plain English summary The purpose of this paper is to describe a patient engagement event designed to create an educational workbook with smokers who drink alcohol at harmful levels. The goal was to create a workbook that combined scientific evidence with patients’ values, preferences, and needs. Fourteen adult smokers who drink alcohol were invited to the Centre for Addiction and Mental Health (CAMH) to take part in a four-hour event to help design the workbook with the CAMH research team. Participants provided their opinions and ideas to create an outline for the workbook, including activities, images, and titles. The workbook – called Self-Awareness – is currently being offered in a smoking cessation program in 221 primary care clinics across Ontario to help smokers quit or reduce their harmful alcohol use. The patient engagement event was a useful way to co-create educational materials that incorporate both scientific research and patient needs. Abstract Background Evidence-based medicine is the integration of best research evidence with clinical expertise and patient values. There are few methodologies on how to design evidence-based programs and resources to include patient values. The latter is an important aspect of patient-centered care, and is essential for patients to trust the recommendations and empower them as consumers to make informed choices. This manuscript describes a participatory research approach to design patient-facing educational materials that incorporate both evidence-based and community-sensitive principles. These materials are intended to support smokers to reduce or stop harmful alcohol consumption. Methods Adult smokers who report consuming alcohol were invited to a co-creation meeting at the Centre for Addiction and Mental Health’s Nicotine Dependence Service to guide the adaptation of evidence-based materials. The four-hour event consisted of individual reflections, group discussions, and consensus-building interactions. Detailed notes were taken and then incorporated into the material. Results Fourteen individuals participated in the event. The end product was a descriptive outline of an educational resource – entitled Self-Awareness – incorporating material from evidence-based workbooks and patient-driven features. Participants collaboratively selected the resource’s content, structure, and titles. Conclusions This model describes a participatory research method that emphasizes the value of the patient perspective; preliminary evidence finds this adaptation approach can increase the adoption of resources. The process described in this article could be replicated in other settings to co-create evidence-based resources, interventions, and programs that reflect the needs of the community. Trial registration ClinicalTrials.gov NCT03108144 . Retrospectively registered 11 April 2017

Combining alcohol interventions with tobacco addictions treatment in primary care—the COMBAT study: a pragmatic cluster randomized trial

Abstract Background Tobacco and alcohol use present multiplicative risk for aerodigestive cancers. Reducing alcohol consumption improves smoking cessation outcomes and reduces cancer risk. Risky alcohol consumption and smoking are often treated separately despite concurrent treatment potentially leading to better outcomes for each. However, no rapidly scalable program exists for combined interventions in primary care clinics spread across wide geographic areas. This cluster randomized trial aims to report on the effects of a novel clinical decision support system (CDSS) on intervention rates by primary care practitioners addressing risky alcohol use in a smoking cessation program. Methods/design We will be implementing a clinical decision support system (CDSS) in 221 primary care sites participating in the Smoking Treatment for Ontario Patients (STOP) program across Ontario, Canada. Sites will be blindly allocated to one of two clinical decision support systems guiding practitioners to provide a risky alcohol use intervention to smokers attempting to quit using nicotine replacement therapy (NRT). Risky alcohol use is defined as drinking above the Canadian Cancer Society’s low-risk drinking guidelines. Primary analysis will measure the proportion of risky drinkers offered an alcohol intervention in each CDSS arm at baseline. Patients will be contacted by phone or email to track smoking cessation and alcohol consumption rates at 6- and 12-month follow-up. Discussion Upon completion of the trial, the effect of different clinical decision support systems on practitioner behaviour, and on client tobacco and alcohol use, will be discussed. If the CDSS successfully promotes SBIRT for risky alcohol use in a primary care setting and/or improves patient-level outcomes, including smoking cessation rates and alcohol use reduction, this tool can be used as a model for other web-based behaviour change interventions integrated into primary care practice. Trial registration ClinicalTrials.gov NCT0310814

The effect of a clinical decision support system on prompting an intervention for risky alcohol use in a primary care smoking cessation program: a cluster randomized trial

Abstract Background Clinical decision support systems (CDSSs) may promote practitioner adherence to evidence-based guidelines. This study examined if the addition of a CDSS influenced practitioner delivery of a brief intervention with treatment-seeking smokers who were drinking above recommended alcohol consumption guidelines, compared with practitioners who do not receive a CDSS prompt. Methods This was a cluster randomized controlled trial conducted in primary health care clinics across Ontario, Canada, implementing the Smoking Treatment for Ontario Patients (STOP) smoking cessation program. Clinics randomized to the intervention group received a prompt when a patient reported consuming alcohol above the Canadian Cancer Society (CCS) guidelines; the control group did not receive computer alerts. The primary outcome was an offer of an appropriate educational alcohol resource, an alcohol reduction workbook for patients drinking above the CCS guidelines, and an abstinence workbook to patients scoring above 20 points in the AUDIT screening tool; the secondary outcome was patient acceptance of the resource. The tertiary outcome was patient abstinence from smoking, and alcohol consumption within CCS guidelines, at 6-month follow-up. Results were analyzed using a generalized estimation approach for fitting logistic regression using a population-averaged method. Results Two hundred and twenty-one clinics across Ontario were randomized for this study; 110 to the intervention arm and 111 to the control arm. From the 15,222 patients that enrolled in the smoking cessation program, 15,150 (99.6% of patients) were screened for alcohol use and 5715 patients were identified as drinking above the CCS guidelines. No statistically significant difference between groups was seen in practitioner offer of an educational alcohol resource to appropriate patients (OR = 1.19, 95% CI 0.88–1.64, p = 0.261) or in patient abstinence from smoking and drinking within the CCS guidelines at 6-month follow-up (OR = 0.93, 95% CI 0.71–1.22, p = 0.594). However, a significantly greater proportion of patients in the intervention group accepted the alcohol resource offered to them by their practitioner (OR = 1.48, 95% CI 1.01–2.16, p = 0.045). Conclusion A CDSS may not increase the likelihood of practitioners offering an educational alcohol resource, though it may have influenced patients’ acceptance of the resource. Trial registration This trial is registered with ClinicalTrials.gov, number NCT03108144 , registered on April 11, 2017, “retrospectively registered”