Current Role at Stanford

Primary role at Stanford is to support the Strategic Plan for Research in the Department of Emergency Medicine.
Goals include building research infrastructure to support all EMed investigators, leveraging the strength of Stanford University to produce high-impact and innovative emergency care research, and supporting the efforts to become a national leader in academic emergency medicine research.

Also involved with supporting the efforts of the Twin Registry at Stanford - a valuable resource for research into the influences of genetics on a variety of traits and conditions.

Education & Certifications

  • B.A., University of California, Santa Barbara, Biology
  • M.A, San Jose State University, Health Science

All Publications

  • Outcomes from a patient-centered residential treatment plan for tobacco dependence. Mayo Clinic proceedings Hodgkin, J. E., Sachs, D. P., Swan, G. E., Jack, L. M., Titus, B. L., Waldron, S. J., Sachs, B. L., Brigham, J. 2013; 88 (9): 970-6


    St. Helena Hospital launched the first US residential stop-smoking program, The St. Helena Center for a Smoke-Free Life, in 1969. This observational report describes the center's treatment outcome rate for using a patient-centered approach to the use of tobacco dependence medications and behavioral treatment for patients who participated in the program from January 1, 2005 through December 31, 2007. A total of 284 patients used long-acting (nicotine patch, bupropion, and varenicline) and/or short-acting medications (nicotine nasal spray, nicotine gum, nicotine lozenge, and nicotine oral inhaler) alone or in combination during treatment and after discharge. Seven patients chose to use no medications. Patients using nicotine patch received a mean ± SD dose of 33.3±15.7 mg of nicotine in 16 hours (range, 5-90 mg). The 12-month 7-day point prevalence smoking abstinence rate after participation in the intensive, 1-week, residential program was 57.0%. Recommendations are discussed for future research and for implementing aspects of the St. Helena program in other treatment settings.

    View details for DOI 10.1016/j.mayocp.2013.05.027

    View details for PubMedID 24001489

  • The Twin Research Registry at SRI International. Twin research and human genetics : the official journal of the International Society for Twin Studies Krasnow, R. E., Jack, L. M., Lessov-Schlaggar, C. N., Bergen, A. W., Swan, G. E. 2013; 16 (1): 463-70


    The Twin Research Registry (TRR) at SRI International is a community-based registry of twins established in 1995 by advertising in local media, mainly on radio stations and in newspapers. As of August 2012, there are 3,120 same- and opposite-sex twins enrolled; 86% are 18 years of age or older (mean age 44.9 years, SD 16.9 years) and 14% less than 18 years of age (mean age 8.9 years, SD 4.5); 67% are female, and 62% are self-reported monozygotic (MZ). More than 1,375 twins have participated in studies over the last 15 years in collaboration with the University of California Medical Center in San Francisco, the University of Texas MD Anderson Cancer Center, and the Stanford University School of Medicine. Each twin completes a registration form with basic demographic information either online at the TRR Web site or during a telephone interview. Contact is maintained with members by means of annual newsletters and birthday cards. The managers of the TRR protect the confidentiality of twin data with established policies; no information is given to other researchers without prior permission from the twins; and all methods and procedures are reviewed by an Institutional Review Board. Phenotypes studied thus far include those related to nicotine metabolism, mutagen sensitivity, pain response before and after administration of an opioid, and a variety of immunological responses to environmental exposures, including second-hand smoke and vaccination for seasonal influenza virus and Varicella zoster virus. Twins in the TRR have participated in studies of complex, clinically relevant phenotypes that would not be feasible to measure in larger samples.

    View details for DOI 10.1017/thg.2012.81

    View details for PubMedID 23084148

    View details for PubMedCentralID PMC4586265

  • Asthma Discordance in Twins Is Linked to Epigenetic Modifications of T Cells PLOS ONE Runyon, R. S., Cachola, L. M., Rajeshuni, N., Hunter, T., Garcia, M., Ahn, R., Lurmann, F., Krasnow, R., Jack, L. M., Miller, R. L., Swan, G. E., Kohli, A., Jacobson, A. C., Nadeau, K. C. 2012; 7 (11)


    T cells mediate the inflammatory responses observed in asthma among genetically susceptible individuals and have been suspected to be prone to epigenetic regulation. However, these relationships are not well established from past clinical studies that have had limited capacity to control for the effects of variable genetic predisposition and early environmental exposures. Relying on a cohort of monozygotic twins discordant for asthma we sought to determine if epigenetic modifications in T cells were associated with current asthma and explored whether such modifications were associated with second hand smoke exposures. Our study was conducted in a monozygotic twin cohort of adult twin pairs (n = 21) all discordant for asthma. Regulatory T cell (Treg) and effector T cell (Teff) subsets were assessed for levels of cellular function, protein expression, gene expression and CpG methylation within Forkhead box P3 (FOXP3) and interferon gamma-γ (IFNγ) loci. Comparisons by asthma and current report of exposure to second hand smoke were made. Treg from asthmatic discordant twins demonstrated decreased FOXP3 protein expression and impaired Treg function that was associated with increased levels of CpG methylation within the FOXP3 locus when compared to their non-asthmatic twin partner. In parallel, Teff from discordant asthmatic twins demonstrated increased methylation of the IFNγ locus, decreased IFNγ expression and reduced Teff function when compared to Teff from the non-asthmatic twin. Finally, report of current exposure to second hand smoke was associated with modifications in both Treg and Teff at the transcriptional level among asthmatics. The results of the current study provide evidence for differential function of T cell subsets in monozygotic twins discordant for asthma that are regulated by changes in DNA methylation. Our preliminary data suggest exposure to second hand smoke may augment the modified T cell responses associated with asthma.

    View details for DOI 10.1371/journal.pone.0048796

    View details for Web of Science ID 000312376100014

    View details for PubMedID 23226205

    View details for PubMedCentralID PMC3511472

  • Varenicline for smoking cessation: nausea severity and variation in nicotinic receptor genes. The pharmacogenomics journal Swan, G. E., Javitz, H. S., Jack, L. M., Wessel, J., Michel, M., Hinds, D. A., Stokowksi, R. P., McClure, J. B., Catz, S. L., Richards, J., Zbikowski, S. M., Deprey, M., McAfee, T., Conti, D. V., Bergen, A. W. 2012; 12 (4): 349-58


    This study evaluated association between common and rare sequence variants in 10 nicotinic acetylcholine receptor subunit genes and the severity of nausea 21 days after initiating the standard, Food and Drug Administration-approved varenicline regimen for smoking cessation. A total of 397 participants from a randomized clinical effectiveness trial with complete clinical and DNA resequencing data were included in the analysis (mean age=49.2 years; 68.0% female). Evidence for significant association between common sequence variants in CHRNB2 and nausea severity was obtained after adjusting for age, gender and correlated tests (all P(ACT)<0.05). Individuals with the minor allele of CHRNB2 variants experienced less nausea than did those without the minor allele, consistent with previously reported findings for CHRNB2 and the occurrence of nausea and dizziness as a consequence of first smoking attempt in adolescents, and with the known neurophysiology of nausea. As nausea is the most common reason for discontinuance of varenicline, further pharmacogenetic investigations are warranted.

    View details for DOI 10.1038/tpj.2011.19

    View details for PubMedID 21606948

    View details for PubMedCentralID PMC3405554

  • Adherence to varenicline in the COMPASS smoking cessation intervention trial. Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco Catz, S. L., Jack, L. M., McClure, J. B., Javitz, H. S., Deprey, M., Zbikowski, S. M., McAfee, T., Richards, J., Swan, G. E. 2011; 13 (5): 361-8


    Patient adherence to smoking cessation medications can impact their effectiveness. It is important to understand the extent to which prescribed medications are actually taken by smokers, how this influences smoking cessation outcomes, and what factors may influence adherence.Smokers recruited from a large health plan were randomized to receive different modes of cessation counseling in combination with varenicline (Swan, G. E., McClure, J. B., Jack, L. M., Zbikowski, S. M., Javitz, H. S., Catz, S. L., et al. 2010.Behavioral counseling and varenicline treatment for smoking cessation. American Journal of Preventive Medicine, 38, 482-490). One thousand one hundred and sixty-one participants were mailed a 28-day varenicline supply when they set a quit date and were able to request up to two refills from the health plan pharmacy at no cost. Pharmacy fill records were obtained and telephone surveys completed at baseline, 21 days, 12 weeks, and 6 months post target quit date.Good adherence to varenicline (≥80% of days taken) was associated with a twofold increase in 6-month quit rates compared with poor adherence (52% vs. 25%). Smokers were more likely than nonsmokers to stop varenicline early. Purposeful nonadherence was associated with smoking at 12 weeks and was predicted in multivariate analyses by age, gender, adherence self-efficacy, and initial medication side effect severity.Innovative methods for increasing adherence to smoking cessation medications are needed, particularly early in the quit process. Simple metrics of adherence such as number of days cessation medication is taken can and should be routinely incorporated in effectiveness trials and reported to advance future attempts to understand and reduce nonadherence.

    View details for DOI 10.1093/ntr/ntr003

    View details for PubMedID 21350041

    View details for PubMedCentralID PMC3082504

  • Utilization of services in a randomized trial testing phone- and web-based interventions for smoking cessation. Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco Zbikowski, S. M., Jack, L. M., McClure, J. B., Deprey, M., Javitz, H. S., McAfee, T. A., Catz, S. L., Richards, J., Bush, T., Swan, G. E. 2011; 13 (5): 319-27


    Phone counseling has become standard for behavioral smoking cessation treatment. Newer options include Web and integrated phone-Web treatment. No prior research, to our knowledge, has systematically compared the effectiveness of these three treatment modalities in a randomized trial. Understanding how utilization varies by mode, the impact of utilization on outcomes, and predictors of utilization across each mode could lead to improved treatments.One thousand two hundred and two participants were randomized to phone, Web, or combined phone-Web cessation treatment. Services varied by modality and were tracked using automated systems. All participants received 12 weeks of varenicline, printed guides, an orientation call, and access to a phone supportline. Self-report data were collected at baseline and 6-month follow-up.Overall, participants utilized phone services more often than the Web-based services. Among treatment groups with Web access, a significant proportion logged in only once (37% phone-Web, 41% Web), and those in the phone-Web group logged in less often than those in the Web group (mean = 2.4 vs. 3.7, p = .0001). Use of the phone also was correlated with increased use of the Web. In multivariate analyses, greater use of the phone- or Web-based services was associated with higher cessation rates. Finally, older age and the belief that certain treatments could improve success were consistent predictors of greater utilization across groups. Other predictors varied by treatment group.Opportunities for enhancing treatment utilization exist, particularly for Web-based programs. Increasing utilization more broadly could result in better overall treatment effectiveness for all intervention modalities.

    View details for DOI 10.1093/ntr/ntq257

    View details for PubMedID 21330267

    View details for PubMedCentralID PMC3082503

  • Cost-effectiveness of varenicline and three different behavioral treatment formats for smoking cessation. Translational behavioral medicine Javitz, H. S., Zbikowski, S. M., Deprey, M., McAfee, T. A., McClure, J. B., Richards, J., Catz, S. L., Jack, L. M., Swan, G. E. 2011; 1 (1): 182-190


    There is a lack of evidence of the relative cost-effectiveness of proactive telephone counseling (PTC) and Web-based delivery of smoking cessation services in conjunction with pharmacotherapy. We calculated the differential cost-effectiveness of three behavioral smoking cessation modalities with varenicline treatment in a randomized trial of current smokers from a large health system. Eligible participants were randomized to one of three smoking cessation interventions: Web-based counseling (n=401), PTC (n=402), or combined PTC-Web counseling (n=399). All participants received a standard 12-week course of varenicline. The primary outcome was a 7-day point prevalent nonsmoking at the 6month follow-up. The Web intervention was the least expensive followed by the PTC and PTC-Web groups. Costs per additional 6-month nonsmoker and per additional lifetime quitter were $1,278 and $2,601 for Web, $1,472 and $2,995 for PTC, and $1,617 and $3,291 for PTC-Web. Cost per life-year (LY) and quality-adjusted life-year (QALY) saved were $1,148 and $1,136 for Web, $1,320 and $1,308 for PTC, and $1,450 and $1,437 for PTC-Web. Based on the cost per LY and QALY saved, these interventions are among the most cost-effective life-saving medical treatments. Web, PTC, and combined PTC-Web treatments were all highly cost-effective, with the Web treatment being marginally more cost-effective than the PTC or combined PTC-Web treatments.

    View details for DOI 10.1007/s13142-010-0009-8

    View details for PubMedID 21731592

    View details for PubMedCentralID PMC3124766

  • Resequencing of nicotinic acetylcholine receptor genes and association of common and rare variants with the Fagerström test for nicotine dependence. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology Wessel, J., McDonald, S. M., Hinds, D. A., Stokowski, R. P., Javitz, H. S., Kennemer, M., Krasnow, R., Dirks, W., Hardin, J., Pitts, S. J., Michel, M., Jack, L., Ballinger, D. G., McClure, J. B., Swan, G. E., Bergen, A. W. 2010; 35 (12): 2392-402


    Common single-nucleotide polymorphisms (SNPs) at nicotinic acetylcholine receptor (nAChR) subunit genes have previously been associated with measures of nicotine dependence. We investigated the contribution of common SNPs and rare single-nucleotide variants (SNVs) in nAChR genes to Fagerström test for nicotine dependence (FTND) scores in treatment-seeking smokers. Exons of 10 genes were resequenced with next-generation sequencing technology in 448 European-American participants of a smoking cessation trial, and CHRNB2 and CHRNA4 were resequenced by Sanger technology to improve sequence coverage. A total of 214 SNP/SNVs were identified, of which 19.2% were excluded from analyses because of reduced completion rate, 73.9% had minor allele frequencies <5%, and 48.1% were novel relative to dbSNP build 129. We tested associations of 173 SNP/SNVs with the FTND score using data obtained from 430 individuals (18 were excluded because of reduced completion rate) using linear regression for common, the cohort allelic sum test and the weighted sum statistic for rare, and the multivariate distance matrix regression method for both common and rare SNP/SNVs. Association testing with common SNPs with adjustment for correlated tests within each gene identified a significant association with two CHRNB2 SNPs, eg, the minor allele of rs2072660 increased the mean FTND score by 0.6 Units (P=0.01). We observed a significant evidence for association with the FTND score of common and rare SNP/SNVs at CHRNA5 and CHRNB2, and of rare SNVs at CHRNA4. Both common and/or rare SNP/SNVs from multiple nAChR subunit genes are associated with the FTND score in this sample of treatment-seeking smokers.

    View details for DOI 10.1038/npp.2010.120

    View details for PubMedID 20736995

    View details for PubMedCentralID PMC3055324

  • Smoking outcome by psychiatric history after behavioral and varenicline treatment. Journal of substance abuse treatment McClure, J. B., Swan, G. E., Catz, S. L., Jack, L., Javitz, H., McAfee, T., Deprey, M., Richards, J., Zbikowski, S. M. 2010; 38 (4): 394-402


    Treatment outcomes were compared across smokers enrolled in the COMPASS cessation trial with (positive psychiatric history [PH+], n = 271) and without (PH-, n = 271) a diagnosis of PH based on medical record evidence of anxiety, depression, psychotic disorder, or bipolar disorder. Everyone received behavioral counseling plus varenicline and was followed for 6 months post quit date. PH+ smokers took varenicline for fewer days on average (59.4 vs. 68.5, p < or = .01) but did not differ in their use of behavioral treatment. PH+ smokers were more likely to report anxiety and depression, but side-effect intensity ratings did not differ after adjusting for multiple comparisons. Overall, all side effects were rated as moderate intensity or less. Groups had similar 30-day abstinence rates at 6 months (31.5% PH+ vs. 35.4% PH-, p = .35). In sum, having a psychiatric diagnosis in this trial did not predict worse treatment outcome or worse treatment side effects.

    View details for DOI 10.1016/j.jsat.2010.03.007

    View details for PubMedID 20363092

    View details for PubMedCentralID PMC2860053

  • Behavioral counseling and varenicline treatment for smoking cessation. American journal of preventive medicine Swan, G. E., McClure, J. B., Jack, L. M., Zbikowski, S. M., Javitz, H. S., Catz, S. L., Deprey, M., Richards, J., McAfee, T. A. 2010; 38 (5): 482-90


    Smoking remains the primary preventable cause of death and illness in the U.S. Effective, convenient treatment programs are needed to reduce smoking prevalence.This study compared the effectiveness of three modalities of a behavioral smoking-cessation program in smokers using varenicline.Current treatment-seeking smokers (n=1202) were recruited from a large healthcare organization between October 2006 and October 2007. Eligible participants were randomized to one of three smoking-cessation interventions: web-based counseling (n=401); proactive telephone-based counseling (PTC; n=402); or combined PTC and web counseling (n=399). All participants received a standard 12-week FDA-approved course of varenicline. Self-report determined the primary outcomes (7-day point prevalent abstinence at 3- and 6-month follow-ups); the number of days varenicline was taken; and treatment-related symptoms. Behavioral measures determined utilization of both the web- and Phone-based counseling.Intent-to-treat analyses revealed relatively high percentages of abstinence at 3 months (38.9%, 48.5%, 43.4%) and at 6 months (30.7%, 34.3%, 33.8%) for the web, PTC, and PTC-web groups, respectively. The PTC group had a significantly higher percentage of abstinence than the web group at 3 months (OR=1.48, 95% CI=1.12, 1.96), but no between-group differences in abstinence outcomes were seen at 6 months.Phone counseling had greater treatment advantage for early cessation and appeared to increase medication adherence, but the absence of differences at 6 months suggests that any of the interventions hold promise when used in conjunction with varenicline.

    View details for DOI 10.1016/j.amepre.2010.01.024

    View details for PubMedID 20409497

    View details for PubMedCentralID PMC2879135

  • Clinical trial participant characteristics and saliva and DNA metrics. BMC medical research methodology Nishita, D. M., Jack, L. M., McElroy, M., McClure, J. B., Richards, J., Swan, G. E., Bergen, A. W. 2009; 9: 71


    Clinical trial and epidemiological studies need high quality biospecimens from a representative sample of participants to investigate genetic influences on treatment response and disease. Obtaining blood biospecimens presents logistical and financial challenges. As a result, saliva biospecimen collection is becoming more frequent because of the ease of collection and lower cost. This article describes an assessment of saliva biospecimen samples collected through the mail, trial participant demographic and behavioral characteristics, and their association with saliva and DNA quantity and quality.Saliva biospecimens were collected using the Oragene(R) DNA Self-Collection Kits from participants in a National Cancer Institute funded smoking cessation trial. Saliva biospecimens from 565 individuals were visually inspected for clarity prior to and after DNA extraction. DNA samples were then quantified by UV absorbance, PicoGreen(R), and qPCR. Genotyping was performed on 11 SNPs using TaqMan(R) SNP assays and two VNTR assays. Univariate, correlation, and analysis of variance analyses were conducted to observe the relationship between saliva sample and participant characteristics.The biospecimen kit return rate was 58.5% among those invited to participate (n = 967) and 47.1% among all possible COMPASS participants (n = 1202). Significant gender differences were observed with males providing larger saliva volume (4.7 vs. 4.5 ml, p = 0.019), samples that were more likely to be judged as cloudy (39.5% vs. 24.9%, p < 0.001), and samples with greater DNA yield as measured by UV (190.0 vs. 138.5, p = 0.002), but reduced % human DNA content (73.2 vs. 77.6 p = 0.005) than females. Other participant characteristics (age, self-identified ethnicity, baseline cigarettes per day) were associated with saliva clarity. Saliva volume and saliva and DNA clarity were positively correlated with total DNA yield by all three quantification measurements (all r > 0.21, P < 0.001), but negatively correlated with % human DNA content (saliva volume r = -0.148 and all P < 0.010). Genotyping completion rate was not influenced by saliva or DNA clarity.Findings from this study show that demographic and behavioral characteristics of smoking cessation trial participants have significant associations with saliva and DNA metrics, but not with the performance of TaqMan(R) SNP or VNTR genotyping assays.COMPASS; registered as NCT00301145 at

    View details for DOI 10.1186/1471-2288-9-71

    View details for PubMedID 19874586

    View details for PubMedCentralID PMC2776600

  • Impact of symptoms experienced by varenicline users on tobacco treatment in a real world setting. Journal of substance abuse treatment Halperin, A. C., McAfee, T. A., Jack, L. M., Catz, S. L., McClure, J. B., Deprey, T. M., Richards, J., Zbikowski, S. M., Swan, G. E. 2009; 36 (4): 428-34


    This article examines reported symptoms, nonsmoking rates, and medication use among 1,018 smokers using varenicline in a randomized trial comparing three forms of behavioral support for smoking cessation (phone, Web, or phone + Web). One month after beginning varenicline, 168 people (17%) had discontinued the medication. Most (53%) quit due to side effects and other symptoms. The most common side effect among all users was nausea (reported by 57% of users). At 1 month post medication initiation, those not taking varenicline were more likely to report smoking than those who continued the medication (57% vs. 16%, p < .001). Women reported more symptoms but did not discontinue medication at higher rates. Participants who received any telephone counseling (n = 681) were less likely to discontinue their medication than those with Web support only (15% vs. 21%, p < .01). Counseling may improve tolerance of this medication and reduce the rate of discontinuation due to side effects.

    View details for DOI 10.1016/j.jsat.2008.09.001

    View details for PubMedID 19004600

    View details for PubMedCentralID PMC2776715

  • Mood, side-effects and smoking outcomes among persons with and without probable lifetime depression taking varenicline. Journal of general internal medicine McClure, J. B., Swan, G. E., Jack, L., Catz, S. L., Zbikowski, S. M., McAfee, T. A., Deprey, M., Richards, J., Javitz, H. 2009; 24 (5): 563-9


    Varenicline may be associated with greater mood disturbance and side-effects among smokers with psychiatric history, but empirical evidence is limited. Differential treatment effectiveness by psychiatric history may also exist.To compare mood, prevalence and intensity of treatment side-effects, and abstinence among people with a probable history of major depression (DH+) or not (DH-) who took varenicline and received behavioral smoking cessation treatment.Smokers participated in a randomized behavioral intervention effectiveness trial. Treatment side-effects and outcomes were compared between DH+ and DH- participants (n = 1,117) at 21 [corrected] days and 3 months after the target quit date.Smokers recruited from a large regional health plan.Change in stress and depression scores, prevalence and intensity of treatment side-effects, and abstinence rates.All side-effects averaged moderate intensity or less and were similar across DH groups, except DH+'s endorsed slightly worse confusion, nausea (adjusted P = 0.04) and trouble sleeping (adjusted P = 0.008) at 21 days. Depression and stress scores declined in both DH groups and an equal proportion of each evidenced new/worsening depressive symptoms. Despite few differences in symptom intensity, more DH+ participants reported recent tension/agitation, irritability/anger, confusion, and depression at 21 days (adjusted P < 0.05), and depression and anxiety (adjusted P < 0.01) at three months. Nonsmoking rates did not differ by DH group at follow-up.While some group differences were noted, DH+ smokers did not report qualitatively worse neuropsychiatric symptoms, more new/worsening mood disturbance, or differential abstinence rates compared to DH- smokers.

    View details for DOI 10.1007/s11606-009-0926-8

    View details for PubMedID 19238488

    View details for PubMedCentralID PMC2669860

  • Canary in a coal mine? Interest in bupropion SR use among smokers in the COMPASS trial. Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco McClure, J. B., Jack, L., Deprey, M., Catz, S., McAfee, T., Zbikowski, S., Westbrook, E., Swan, G. 2008; 10 (12): 1815-6

    View details for DOI 10.1080/14622200802488358

    View details for PubMedID 19023832

  • Predictors of 12-month outcome in smokers who received bupropion sustained-release for smoking cessation. CNS drugs Swan, G. E., Jack, L. M., Javitz, H. S., McAfee, T., McClure, J. B. 2008; 22 (3): 239-56


    To examine heterogeneity in outcome at 12 months following 8 weeks of treatment for smoking cessation with bupropion sustained-release (SR) 150 or 300 mg/day combined with behavioural counselling.Smokers were recruited from a large healthcare system and then randomized to receive either bupropion SR 150 mg/day (n = 763) or 300 mg/day (n = 761) taken for 8 weeks in combination with either proactive telephone counselling or a tailored mail approach.A comprehensive set of relevant individual pretreatment and treatment characteristics was included in the analysis. Smoking outcome at 12 months was defined as point-prevalence of any regular self-reported smoking within the 7 days prior to follow-up contact. Classification and regression tree analysis identified subgroups that varied with respect to likelihood of being nonsmokers at 12 months. Seven subgroups were identified among those receiving bupropion SR 150 mg/day (proportion of nonsmokers at 12 months ranged from 13.7% to 43.5%) and eight subgroups among those receiving bupropion SR 300 mg/day (proportion of nonsmokers at 12 months ranged from 9.6% to 51.7%). In the 150-mg/day group, those with the lowest rate reported no previous quit attempt of 1 month or more in duration while those with the highest rate all reported previous quit attempts of 1 month or longer. In the 300 mg/day group, those with the lowest rate had very high levels of dependence while those with the highest rate were more highly educated and smoked at a lower level. Across all subgroups, cost per 12-month quitter ranged from a low of USD302 to a high of USD2,502.These results indicate the presence of a substantial amount of variation in outcome following treatment with both dosages of bupropion SR, with substantial cost consequences. Variation in outcome could be reduced by providing treatments tailored to subgroups of individuals who are at exceptionally high risk for smoking following a quit attempt.

    View details for DOI 10.2165/00023210-200822030-00004

    View details for PubMedID 18278978

  • Adolescent smoking trajectories and nicotine dependence. Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco Lessov-Schlaggar, C. N., Hops, H., Brigham, J., Hudmon, K. S., Andrews, J. A., Tildesley, E., McBride, D., Jack, L. M., Javitz, H. S., Swan, G. E. 2008; 10 (2): 341-51


    The present study correlates empirically constructed prospective adolescent smoking trajectories with indicators of nicotine dependence assessed in adolescence and in adulthood. Excluding individuals who reported no smoking during repeat assessment (nonadopters), we identified five smoking trajectory groups: experimenters (n=116, 48.5%), late increasers (n=39, 16.3%), early increasers (n=37, 15.5%), quitters (n=22, 9.2%), and persistent smokers (n=25, 10.5%). Higher frequency of nicotine dependence symptoms in adolescence occurred in the quitters and persistent smokers groups, who smoked at higher levels relative to the experimenters, late increasers, and early increasers groups, who reported a similar frequency of nicotine dependence symptoms and smoked at low levels. Lifetime nicotine dependence was assessed in adulthood in lifetime daily smokers using the Fagerström Test for Nicotine Dependence (FTND) and the Nicotine Dependence Scale (NDS). Lifetime FTND levels were similar across trajectory groups. Relative to experimenters, all remaining smoking trajectory groups had higher NDS levels that were similar to one another. These results suggest that higher levels of adolescent nicotine dependence were associated with heavier smoking trajectory groups, and that regardless of trajectory group membership, smoking more than a few cigarettes per week throughout adolescence resulted in similar levels of lifetime nicotine dependence as measured by the FTND and NDS.

    View details for DOI 10.1080/14622200701838257

    View details for PubMedID 18236299

  • Joint effect of dopaminergic genes on likelihood of smoking following treatment with bupropion SR. Health psychology : official journal of the Division of Health Psychology, American Psychological Association Swan, G. E., Jack, L. M., Valdes, A. M., Ring, H. Z., Ton, C. C., Curry, S. J., McAfee, T. 2007; 26 (3): 361-8


    To determine the relationship between joint variation in 2 dopaminergic genes and the likelihood of nonsmoking following treatment with bupropion sustained release (SR).Three hundred twenty-three participants in a bupropion SR smoking cessation effectiveness trial with 12-month follow-up were genotyped for variants of dopamine receptor gene DRD2 and dopamine transporter SLC6A3.Self-reported 7-day point prevalence of nonsmoking.Neither genotype alone was associated with 7-day point-prevalent nonsmoking at the 12-month follow-up. However, in the presence of the DRD2 A1 allele, SLC6A3 status was significantly associated with the likelihood of nonsmoking at the 12-month follow-up (individuals with DRD2 A1+ and SLC6A3 9- were more likely to be smoking). In the absence of the DRD2 A1 allele, the association between SLC6A3 status and nonsmoking was nonsignificant.Although these results are suggestive, a more compelling test is needed of the hypothesis that dopaminergic gene interaction underlies, in part, the likelihood of smoking following treatment with bupropion SR. Most likely this will come from larger studies involving prospective randomization to treatment based on genotype.

    View details for DOI 10.1037/0278-6133.26.3.361

    View details for PubMedID 17500623

  • Financial burden of tobacco use: an employer's perspective. Clinics in occupational and environmental medicine Javitz, H. S., Zbikowski, S. M., Swan, G. E., Jack, L. M. 2006; 5 (1): 9-29, vii


    To assist in determining whether employer-sponsored smoking cessation programs can be justified on cost-effectiveness grounds, a review was performed to examine the costs imposed on employers by smoking and the extent to which employers can recover those costs through successful smoking cessation programs. The magnitude of the costs (or cost savings) imposed by employee tobacco use depends on workplace factors, including medical coverage (before and after retirement), disability and life insurance benefits, level of exposure to workplace pollutants associated with smoking-related diseases, employee turnover rate, current smoke-free area policy, smoking breaks policy, cost of providing smoking areas, and type of retirement pension plan.

    View details for DOI 10.1016/j.coem.2005.10.007

    View details for PubMedID 16446251

  • Dopamine receptor DRD2 genotype and smoking cessation outcome following treatment with bupropion SR. The pharmacogenomics journal Swan, G. E., Valdes, A. M., Ring, H. Z., Khroyan, T. V., Jack, L. M., Ton, C. C., Curry, S. J., McAfee, T. 2005; 5 (1): 21-9


    The A1 allele of the dopamine D2 receptor gene (DRD2) is associated with a reduced number of dopamine binding sites in the brain and with the increased likelihood of substance abuse and addictive behavior. In a study of smokers enrolled in an open-label, randomized effectiveness trial, we investigated whether variants in the DRD2 receptor gene are associated with smoking cessation outcomes following treatment with a combination of bupropion SR and behavioral counseling. Adherence to treatment and point-prevalent smoking status were assessed at 3 and 12 months, respectively, following a target quit date. Compared to women who carry both A2 alleles, women with at least one A1 allele were more likely to report having stopped taking bupropion due to medication side effects (odds ratio (OR)=1.91, 95% confidence interval (CI)=1.01-3.60; P<0.04) and at 12 months were somewhat more likely to report smoking (OR=0.76, 95% CI=0.56-1.03; P<0.076). Significant associations or trends were not observed in men. In women, individual variability in responsiveness to bupropion-based treatment may be partially due to differences in genetic variants influencing dopamine receptor function.

    View details for DOI 10.1038/sj.tpj.6500281

    View details for PubMedID 15492764

  • Return on investment of different combinations of bupropion SR dose and behavioral treatment for smoking cessation in a health care setting: an employer's perspective. Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research Javitz, H. S., Swan, G. E., Zbikowski, S. M., Curry, S. J., McAfee, T. A., Decker, D., Patterson, R., Jack, L. M. 2004; 7 (5): 535-43


    The net benefit (i.e., benefits minus costs) of sustained-release (SR) bupropion for smoking cessation from an employer's perspective has previously been evaluated in clinical trials including frequent, in-person behavioral counseling and manufacturer recommended dosing but not in actual practice settings and lower dosing.The objective of this research was to determine the return on investment (ROI) and internal rate of return (IRR) from an employer's perspective of two dosing schedules of bupropion SR in combination with behavioral interventions of minimal intensity (tailored mailings, TM) or moderate intensity (proactive telephone calls, PTC) in an actual practice setting.An open-label, randomized trial with 1-year follow-up was conducted in a large health system (Group Health Cooperative) based in Seattle, WA. Participants included 1524 adult smokers interested in quitting smoking. Participants were randomly assigned to receive 150 mg of bupropion SR daily and PTC (n=382), 150 mg of bupropion SR daily and TM (n=381), 300 mg of bupropion SR daily and PTC (n=383) or 300 mg of bupropion SR daily and TM (n=378). Sufficient medications for 8 weeks of dosing were provided to patients. The primary outcome measure of the field trial was self-reported point-prevalence 7-day nonsmoking status at 12 months, and the primary outcome measures of the economic analysis were employer net benefit, employer ROI, and the ROI-associated IRR using 2002 dollars.Using net benefit, the 300-mg/PTC and the 150-mg/PTC treatments were approximately equally preferred. Using ROI or IRR, both the 150-mg/TM and 150-mg/PTC treatments were about equally preferred, with IRR values of 31.7% and 31.4%, respectively. Under a pessimistic scenario regarding effectiveness and costs, 150 mg/PTC became more cost-effective than 150 mg/TM, and employer IRR for 150 mg/PTC was 13%. Under an optimistic scenario IRR exceeded 45% for all treatments.These results suggest that employers can receive competitive returns on investment from sponsoring smoking cessation programs, that 150 mg of bupropion doses yield better returns than 300-mg doses, and that PTC treatments should be preferred to TM if smoking cessation rates in the targeted employee population are lower than those in the study population.

    View details for DOI 10.1111/j.1524-4733.2004.75005.x

    View details for PubMedID 15367249

  • Cost-effectiveness of different combinations of bupropion SR dose and behavioral treatment for smoking cessation: a societal perspective. The American journal of managed care Javitz, H. S., Swan, G. E., Zbikowski, S. M., Curry, S. J., McAfee, T. A., Decker, D. L., Patterson, R., Jack, L. M. 2004; 10 (3): 217-26


    To determine the differential cost effectiveness of 2 dosing regimens of bupropion sustained release (SR) in combination with behavioral interventions of minimal intensity (tailored mailings [TM]) or moderate intensity (proactive telephone calls [PTC]) for smoking cessation in an actual practice setting.Open-label, randomized trial, with 1-year follow-up, conducted in a large health system based in Seattle, Washington.A total of 1524 adult smokers interested in quitting smoking were randomly assigned to receive 150 mg bupropion SR daily and PTC (n = 382), 150 mg bupropion SR daily and TM (n = 381), 300 mg bupropion SR daily and PTC (n = 383), or 300 mg bupropion SR daily and TM (n = 378). Sufficient medication for 8 weeks of dosing was provided to patients. The primary outcome measure was self-reported point-prevalence 7-day nonsmoking status at 12 months after the target quit date.Although the 300-mg dose was associated with a higher 12-month nonsmoking rate relative to the 150-mg dose with both PTC and TM, the additional cost resulted in lower cost effectiveness. The PTC behavioral intervention was more expensive than TM, but the additional effectiveness resulted in almost equivalent cost effectiveness at the 150-mg dose. Costs per additional 12-month nonsmoker (above that expected for placebo) for the 150-mg dose groups averaged 950 dollars and per additional lifetime quitter averaged 1508 dollars; for the 300-mg groups these costs were 1342 dollars and 2129 dollars, respectively. Cost per life-year and quality-adjusted life-years (QALYs) saved varied substantially by age and treatment, but were no greater than 1100 dollars for all treatment groups when averaged across the age and sex distribution for the study population.Although the cost per life-year and QALYs saved were sufficiently low for all doses to rate these smoking cessation interventions as among the most cost effective of life-saving medical treatments, within the regimens tested 150 mg bupropion combined with either PTC or TM was the most cost effective.

    View details for PubMedID 15032259

  • Heterogeneity in 12-month outcome among female and male smokers. Addiction (Abingdon, England) Swan, G. E., Javitz, H. S., Jack, L. M., Curry, S. J., McAfee, T. 2004; 99 (2): 237-50


    To examine heterogeneity in outcome following treatment for smoking cessation with combined bupropion SR and behavioral counseling in women and men.This study included 875 women and 649 men recruited from a large health-care system and randomized to one of four combinations of treatment [two dosage levels of bupropion SR (Zyban, 150 mg and 300 mg) were crossed with two counseling programs of lower and higher intensity to create a four-cell design].A comprehensive set of relevant individual characteristics prior to treatment and treatment characteristics was included in the analysis. Smoking outcome at 12 months was defined as point-prevalence of any regular smoking within the 7 days prior to follow-up contact. Classification and regression tree analysis identified six subgroups in women that ranged in proportion of non-smokers from 9.8% to 42.9% and six subgroups in men that ranged in proportion of non-smokers from 17.3% to 50.0%.These results indicate the presence of a substantial amount of variation in treatment outcome among women and men receiving combined bupropion SR and counseling. Variation in outcome could be reduced by providing treatments tailored to subgroups of individuals who are at exceptionally high risk for smoking following cessation.

    View details for DOI 10.1111/j.1360-0443.2003.00629.x

    View details for PubMedID 14756716

  • Bupropion SR and counseling for smoking cessation in actual practice: predictors of outcome. Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco Swan, G. E., Jack, L. M., Curry, S., Chorost, M., Javitz, H., McAfee, T., Dacey, S. 2003; 5 (6): 911-21


    To date, only one study has been published on individual characteristics associated with outcome following standard treatment with bupropion SR for smoking cessation. To investigate treatment outcome beyond the 6-week end-of-treatment point, the present study examined characteristics associated with more clinically relevant smoking endpoints following treatment with bupropion SR in a large health care system. A total of 1,524 smokers (649 men and 875 women) of average age 45.1 years were randomized to receive one of four combinations of bupropion SR (150 or 300 mg) and behavioral counseling (tailored mailings or proactive telephone counseling) and assessed for point-prevalent smoking status at 3 and 12 months. Multiple logistic regression analyses of potential risk factors for 12-month point-prevalent smoking and for persistent smoking (point-prevalent smoking at both follow-ups) following treatment were conducted for men and women combined and separately. Risk factors for smoking at both endpoints in the combined sample included treatment with tailored mailings, female gender, younger age, higher levels of tobacco dependence, shorter previous quit attempts, previous use of nicotine replacement therapy, and report of current depressive symptoms or lifetime depression. Risk factors for smoking following treatment identified in women only included treatment with the lower dose of bupropion SR, younger age, and higher perceived stress, whereas those that were unique to men included the presence of lifetime depression. The results are discussed in terms of their implications for the need for more effective treatments in general, and the role of individual differences in the likelihood of returning to smoking following treatment for quitting.

    View details for DOI 10.1080/14622200310001646903

    View details for PubMedID 14668075

  • Effectiveness of bupropion sustained release for smoking cessation in a health care setting: a randomized trial. Archives of internal medicine Swan, G. E., McAfee, T., Curry, S. J., Jack, L. M., Javitz, H., Dacey, S., Bergman, K. 2003; 163 (19): 2337-44


    The efficacy of bupropion hydrochloride sustained release (SR) (Zyban) for smoking cessation has been evaluated in clinical trials that included frequent in-person behavioral counseling, but not in actual practice settings.To determine the differential effectiveness of 2 doses of bupropion SR in combination with behavioral interventions of minimal to moderate intensity in an actual practice setting.Open-label randomized trial, with 1 year of follow-up.A large health system (Group Health Cooperative) based in Seattle.Adult smokers (N = 1524) interested in quitting smoking.Participants were randomly assigned to receive 1 of 4 combinations of bupropion SR (150 or 300 mg) and behavioral counseling (minimal or moderate intensity).The primary outcome measure was self-reported point-prevalence 7-day nonsmoking status at 3 and 12 months following the target quit date. Secondary outcomes included adverse and abstinence effects reported since beginning treatment with bupropion SR.At 3 months, a significantly higher rate of nonsmoking was observed among those receiving the larger bupropion SR dose (P=.005). At 12 months, moderate intensity counseling was associated significantly with a higher rate of nonsmoking (P=.001). At 3 months, the higher dose was associated with a significantly increased frequency of self-reported symptoms such as difficulty sleeping (P=.02), difficulty concentrating (P=.02), shakiness/tremor (P=.002), and gastrointestinal problems (P=.005)and a decreased frequency of reported desire to smoke (P=.001).In this actual practice setting, the combination of bupropion SR and minimal or moderate counseling was associated with 1-year quit rates of 23.6% to 33.2%. This suggests that existing health care systems can substantially decrease tobacco use rates among their enrollees if they provide these modest interventions.

    View details for DOI 10.1001/archinte.163.19.2337

    View details for PubMedID 14581254

  • Environmental and genetic determinants of tobacco use: Methodology for a multidisciplinary, longitudinal family-based investigation CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Swan, G. E., Hudmon, K. S., Jack, L. M., Hemberger, K., Carmelli, D., Khroyan, T. V., Ring, H. J., Hops, H., Andrews, J. A., Tildesley, E., McBride, D., Benowitz, N., Webster, C., Wilhelmsen, K. C., Feiler, H. S., Koenig, B., Caron, L., Illes, J., Cheng, L. S. 2003; 12 (10): 994-1005


    This article describes the ongoing collaborative effort of six research teams to operationalize and execute an integrative approach to the study of gene x environment interactions in the development of tobacco dependence. At the core of the project is a longitudinal investigation of social and behavioral risk factors for tobacco use in individuals who were, on average, 13 years of age at intake and for whom smoking outcomes extending from early adolescence to young adulthood have been characterized previously (current average age of the cohort is 29 years). The conceptual framework for the integrative approach and the longitudinal investigation on which the study is based is presented. A description is also provided of the methods used to: (a) recruit participants and families to provide DNA samples and information on tobacco use; (b) assess participants for relevant tobacco-related phenotypes including smoking history, current use of tobacco, and nicotine metabolism; (c) assess the quality of the DNA samples collected from participants for genome-wide scanning and candidate gene analysis; (d) examine several research questions concerning the role of genetic and environmental factors in the onset and maintenance of tobacco use; and (e) ensure adherence to local and federal guidelines for ethical and legal investigations of genotypic associations with tobacco-related phenotypes in families. This investigation is unique among ongoing studies of the genetics of tobacco dependence in the extent to which equal importance has been assigned to both phenotypic and genotypic measurements.

    View details for Web of Science ID 000186153500007

    View details for PubMedID 14578134

    View details for PubMedCentralID PMC2587265

  • Bupropion SR and smoking cessation in actual practice: methods for recruitment, screening, and exclusion for a field trial in a managed-care setting. Preventive medicine Jack, L. M., Swan, G. E., Thompson, E., Curry, S. J., McAfee, T., Dacey, S., Bergman, K. 2003; 36 (5): 585-93


    Little is known about the effectiveness of bupropion SR for smoking cessation outside the context of clinical efficacy trials, where in-person screening and treatment occur at a higher level than provided in a typical health care system. This article describes the methods for recruitment, screening for exclusions, and resulting sample in a field trial of bupropion SR undertaken in a managed-care setting.A total of 2979 telephone interviews were conducted to screen and identify eligible volunteers using a detailed protocol that allowed for consultation with study physicians when necessary. The volunteers' primary care physicians were given the option to override their eligibility, and pharmacy databases were used to verify medication reporting.A total of 1909 (64%) volunteers were considered eligible for the study. The most common reason for exclusion was use of contraindicated medications (32%), followed by recent use of one of the behavioral cessation programs (14%), brain injury that reduced seizure threshold (14%), current depression (14%), and high levels of alcohol use (13%).The methods used in this field trial show that it is possible to enroll subjects in an effectiveness trial that is successful from the standpoint of the consumer, provider, and health care system.

    View details for DOI 10.1016/s0091-7435(03)00011-2

    View details for PubMedID 12689804

  • Self-reported abstinence effects in the first month after smoking cessation Addictive Behaviors Ward, M. M., Swan, G. E., Jack, L. M. 2001; 26 (3): 311-27
  • Relationship of family history scores for stroke and hypertension to quantitative measures of white-matter hyperintensities and stroke volume in elderly males. Neuroepidemiology Reed, T., Kirkwood, S. C., DeCarli, C., Swan, G. E., Miller, B. L., Wolf, P. A., Jack, L. M., Carmelli, D. 2000; 19 (2): 76-86


    White-matter hyperintensities (WMHI) are frequently associated with cerebrovascular risk factors in the elderly, particularly hypertension, and have been interpreted as a subclinical form of ischemic brain damage. WMHI, clinical stroke and blood pressures show significant genetic influences. The objective of this study was to determine whether a relationship exists between family history of stroke and/or hypertension in first degree relatives and WMHI in the elderly. WMHI and stroke (CVA) volumes were quantified from brain MRI performed on 414 white, male twins born between 1917 and 1927 (average age 72.3 +/- 2.9 years). WMHI, adjusted for age and head size, was significantly correlated with the family history score (r = 0.21, p < 0.001). Dividing the family history scores into quintiles revealed significant differences in WMHI by quintile mean (p < 0.05). Subjects in the highest quintile of family history score had the highest mean WMHI. Recalculation of the family history score, by only counting relatives reported to have had a clinical stroke as a positive event, revealed a nonsignificant correlation with WMHI, but the correlation of the family history score with MRI CVA volume was significant (p < 0.05). Stepwise multivariate analysis including ApoE status, current smoking status, smoking packyear history, Doppler ankle/arm blood pressure ratios, current and long term hypertensive status and current systolic and diastolic pressures indicated that the stroke/hypertension family history score was the single best predictor (p < 0.01) of WMHI volumes. Family history was not an independent predictor of CVA volume.

    View details for DOI 10.1159/000026242

    View details for PubMedID 10686532

  • The contribution of genetic influences to measures of lower-extremity function in older male twins. The journals of gerontology. Series A, Biological sciences and medical sciences Carmelli, D., Kelly-Hayes, M., Wolf, P. A., Swan, G. E., Jack, L. M., Reed, T., Guralnik, J. M. 2000; 55 (1): B49-53


    Tests of balance, gait, and endurance were administered to 95 monozygotic (MZ) and 92 dizygotic (DZ), white male twins aged 68 to 79 years who had been born in the United States. Within-twin-pair correlations were calculated for each individual task and for an overall summary performance score. These were subjected to structural equation modeling to determine the contributions of genetic and environmental influences to individual differences in performance scores. MZ intraclass correlations were significant and greater than DZ correlations for the 8-foot walk and the repeated chair stands task, but not for the standing balance task. The heritability of the lower-extremity summary score was 57%, of which 39% was due to additive genetic effects and 18% due to nonadditive effects. In addition, we found that genetic influences contributed primarily to twin similarity in the poorest quartile of performance, whereas shared environmental influences contributed to twin similarity in the best quartile.

    View details for DOI 10.1093/gerona/55.1.b49

    View details for PubMedID 10719763

  • Differential genetic influence for components of memory in aging adult twins. Archives of neurology Swan, G. E., Reed, T., Jack, L. M., Miller, B. L., Markee, T., Wolf, P. A., DeCarli, C., Carmelli, D. 1999; 56 (9): 1127-32


    To investigate the relative proportion of genetic and environmental contributions to verbal memory in community-dwelling World War II veteran twins.The California Verbal Learning Test (CVLT) was administered to 94 monozygotic (MZ) and 89 dizygotic (DZ) elderly male twin pair participants in the fourth examination of the National Heart, Lung, and Blood Institute Twin Study.Subjects voluntarily participated on an outpatient basis at a research or medical center facility in 1 of 4 sites in the United States.Subjects had a mean age of 71.8 years (SD, 2.9 years), a mean educational level of 13.6 years (SD, 2.8 years), and no history of stroke and/or a Mini-Mental State Examination score of 23 or greater.Twin pair similarity in performance on 4 factor analytically derived components of the CVLT measuring verbal learning and memory, response discrimination, learning strategy, and recognition memory.The MZ intraclass correlation was significantly larger than the DZ correlation for verbal learning and memory (I<.001) but not for the other 3 components of memory. Using maximum likelihood methods, the best-fitting genetic model indicated that verbal learning and memory has a substantial genetic component (56% of total variance), whereas response discrimination has a much smaller, although still detectable, genetic component (24% of total variance). There is no evidence of genetic influence on learning strategy or recognition memory.Differential contribution of genetic and environmental influences to specific components of memory suggest that, in this group of elderly male twin pairs, some components may be more amenable to intervention than others.

    View details for DOI 10.1001/archneur.56.9.1127

    View details for PubMedID 10488814

  • Association of midlife blood pressure to late-life cognitive decline and brain morphology. Neurology Swan, G. E., DeCarli, C., Miller, B. L., Reed, T., Wolf, P. A., Jack, L. M., Carmelli, D. 1998; 51 (4): 986-93


    To investigate the association between midlife systolic blood pressure (SBP) and late-life cognitive decline and brain morphology in a sample of community-dwelling elderly men 68 to 79 years of age.Subjects are surviving members from the prospective National Heart, Lung, and Blood Institute Twin Study (intake, 1969 to 1972) who, when examined for a fourth time in 1995 through 1997, underwent brain MRI and repeated assessment of neurobehavioral functioning. Quantification of the MR images determined cerebral volume and total volume of white matter hyperintensities (WMHIs) for 392 subjects. Midlife SBP levels measured in 1970, 1980, and 1985 were used to classify subjects into low, medium, and high midlife SBP categories. A 10-year change in performance on the Mini-Mental State Examination, Digit Symbol Substitution Test, Benton Visual Retention Test, and Verbal Fluency Test was also calculated for these subjects. For all reported analyses, patients were treated as genetically unrelated individuals.Subjects with high midlife SBP experienced a greater decline in cognitive performance and had larger WMHI volumes at follow-up in late life than did those with low midlife SBP. Decreased brain parenchyma and increased WMHI volumes were associated with decline in neurobehavioral functioning as measured in late life independent of age, education, and baseline levels of cognition.Midlife SBP is a significant predictor of both decline in cognitive function and MR volumetric measures of brain atrophy in late life. Because decline in neurobehavioral functioning was associated with decreased brain volume and increased WMHI volume, we conclude that the long-term impact of elevated SBP on decline in late-life neurobehavioral functioning is likely to be mediated through its chronic, negative effect on structural characteristics of the brain.

    View details for DOI 10.1212/wnl.51.4.986

    View details for PubMedID 9781518

  • Evidence for genetic variance in white matter hyperintensity volume in normal elderly male twins STROKE Carmelli, D., Decarli, C., Swan, G. E., Jack, L. M., Reed, T., Wolf, P. A., Miller, B. L. 1998; 29 (6): 1177-1181


    White matter hyperintensities (WMHs), as detected by MRI, are common among the elderly and are frequently interpreted as representing a subclinical form of ischemic brain damage. We used volumetric MR techniques to investigate the contribution of genes and the environment to measures of brain morphology in a sample of community dwelling elderly male twins.Brain MR (1.5 T) scans were obtained from 74 monozygotic (MZ) and 71 dizygotic (DZ), white, male, World War II veteran twins born in the United States and age 68 to 79 when scanned. MR quantification used a previously published semiautomated segmentation algorithm to segment brain images into total brain, cerebrospinal fluid (CSF), and WMH volumes. Twin pair covariances were computed for each measure, and structural equation genetic models were fitted to these data.Total cranial, brain parenchyma, CSF, and WMH volumes were highly correlated in MZ pairs, and correlations in MZ pairs were significantly greater than those in DZ pairs. Structural equation modeling indicated heritabilities of 91%, 92%, and 73%, respectively, for total cranial, brain parenchyma, and WMH volumes. Correction for age and head size reduced the heritability of brain parenchyma to 62% (95% confidence interval, 56% to 68%) and the heritability of WMH volume to 71% (95% confidence interval, 66% to 76%). Proband concordance rates for large amounts of WMH were 61% in MZ pairs and 38% in DZ pairs, compared with a prevalence of 15% in the entire sample.This study is the first to quantify the relative contribution of genetic and individual environmental influences to measures of brain morphology in the elderly.

    View details for Web of Science ID 000073979900016

    View details for PubMedID 9626291

  • Subgroups of smokers with different success rates after use of transdermal nicotine. Addiction (Abingdon, England) Swan, G. E., Jack, L. M., Ward, M. M. 1997; 92 (2): 207-17


    To identify subgroups of smokers with different success rates, we applied "tree-structured survival analysis" (TSSA) to data from a previously published trial of transdermal nicotine. The subjects who received active treatment (14 mg patch, n = 275, or the 21 mg patch, n = 262) constituted the sample for this analysis. Using age, gender, the Fagerstrom Tolerance Questionnaire (FTQ), motivation to quit, number of cigarettes smoked at baseline, and body mass index (BMI) as classification variables, TSSA identified two subgroups within the 14 mg patch group and four subgroups of smokers within the 21 mg patch group. Among those receiving the 14 mg patch, individuals with a BMI greater than 26.4 kg/m2 relapsed sooner than did those with a BMI less than or equal to this value. Within the 21 mg patch group, the survival curve for males was significantly different from that observed in females, with males experiencing a longer time to relapse after treatment than did females. Among females, those with a higher motivation to quit relapsed more slowly than did those women with less motivation to quit. This information may be helpful to clinicians seeking to match specific patients to specific treatments with traditional nicotine in order to maximize treatment outcomes.

    View details for PubMedID 9158232

  • Abstinence effects as predictors of 28-day relapse in smokers Addictive Behaviors Swan, G. E., Ward, M. M., Jack, L. M. 1996; 21 (4): 481-90
  • Ambulatory monitoring of heart rate and blood pressure during the first week after smoking cessation. American journal of hypertension Ward, M. M., Swan, G. E., Jack, L. M., Javitz, H. S., Hodgkin, J. E. 1995; 8 (6): 630-4


    To investigate the timecourse of cardiovascular changes immediately after smoking cessation, 16 subjects wore ambulatory monitors on alternate days during a 1-week residential smoking cessation program. Heart rate was significantly elevated at the time of cessation, then declined steadily until 6 h after cessation, when it reached the level of subsequent nonsmoking days. Systolic and diastolic blood pressures were elevated to a lesser degree for the same period after cessation. The timing of the decline in heart rate and blood pressure was coincident with the timing of an increase in withdrawal symptoms and has implications for laboratory and epidemiologic studies.

    View details for DOI 10.1016/0895-7061(95)00042-N

    View details for PubMedID 7662249

  • Effect of smoking cessation and relapse on cardiovascular levels and reactivity. Psychopharmacology Ward, M. M., Swan, G. E., Jack, L. M., Javitz, H. S. 1994; 114 (1): 147-54


    This study was designed to investigate the effect of smoking cessation on heart rate, blood pressure, and finger temperature absolute levels and reactivity to a range of laboratory challenges. The 148 quitters (mean age = 43.3 years, mean amount smoked = 24.9 cigarettes per day, mean years smoked = 25.2) completed three assessments: an average of 4 +/- 2.8 days before cessation (Exam 1), an average of 2 +/- 1.0 days after cessation (Exam 2), and an average of 20 +/- 5.5 days after cessation (Exam 3). A nonsmoking group (n = 39) was similarly assessed three times to control for effects related to repeated testing. Comparison of group changes from Exam 1 to Exam 2 indicated that smoking cessation produced a significant decrease in heart rate during rest and during all stressors (mean = -8.9 bpm). Those quitters who remained abstinent or smoked occasionally showed minimal changes in heart rate from Exam 2 to Exam 3, but those quitters who returned to their previous smoking level showed a significant increase in heart rate from Exam 2 to Exam 3. None of the indices of cardiovascular reactivity changed across exams, and neither did absolute levels of blood pressure or finger temperature at rest or during stressors. The possible mechanisms producing a selective heart rate decline after smoking cessation in the absence of pressor or vasodilation effects are discussed.

    View details for DOI 10.1007/BF02245456

    View details for PubMedID 7846197

  • Cardiovascular reactivity as a predictor of relapse in male and female smokers. Health psychology : official journal of the Division of Health Psychology, American Psychological Association Swan, G. E., Ward, M. M., Jack, L. M., Javitz, H. S. 1993; 12 (6): 451-8


    This study examined the role of psychophysiological reactivity to general stressors measured before smoking cessation as a predictor of relapse in individuals who quit for a minimum of 12 hr and were then followed for a 12-month interval. The study group consisted of 132 (56.9%) female and 100 (43.1%) male participants in a formal smoking cessation program. The reactivity measures were taken while the Ss were still smoking. Heart rate and blood pressure measurements were taken while Ss were resting, performing mental arithmetic, and delivering a speech and after Ss had been standing for 2 min. In the sample as a whole and for women, a higher level of systolic blood pressure reactivity to the cognitive challenge was associated with a shorter time to relapse (p < .05). In men, greater systolic blood pressure decline to standing was significantly associated with a shorter time to relapse (p < .05).

    View details for DOI 10.1037//0278-6133.12.6.451

    View details for PubMedID 8293728

  • Differential rates of relapse in subgroups of male and female smokers. Journal of clinical epidemiology Swan, G. E., Ward, M. M., Carmelli, D., Jack, L. M. 1993; 46 (9): 1041-53


    Subjects for this study were 265 participants of stop-smoking clinics (mean age = 42.6 years; average number of cigarettes smoked daily = 26.0) who were examined before and immediately after cessation and then followed for 1 year. The objective of this study was to identify subgroups of smokers with different rates of relapse using tree-structured survival analysis, a multivariate approach to classification. Five distinct subgroups that differed with respect to the rate of relapse were identified: (I) subjects (n = 15) with very low precessation cotinine levels (< or = 129 ng/ml), who had an exceptionally low rate of relapse (mean abstinence time = 270 days); (II) women 32 years old and younger (n = 24), who had a very high rate of relapse (mean abstinence time = 30.5 days); (III) women over 32 years old (n = 121), with the next highest rate of relapse (mean abstinence time = 98.9 days); (IV) men 36 years old and younger (n = 31), who had a mean abstinence time of 196.7 days; and (V) men over 36 years old (n = 74), who abstained an average of 130.2 days before relapsing. Relapse curves for all groups (except III vs V) differed significantly from each other, p < 0.05. Results indicate that this approach can identify interactions among individual differences that are variably associated with relapse rates. Identification of relapse subgroups may have important implications for both theories and treatment of smoking relapse.

    View details for DOI 10.1016/0895-4356(93)90172-w

    View details for PubMedID 8263577