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Biomedical subjects

Caryn Lerman

Publications and source records attributed to Caryn Lerman.

At least 73 records · Page 4Linked to original sources

Subjective effects of an initial dose of nicotine nasal spray predict treatment outcome.

RATIONALE: Nicotine nasal spray (NS) is recommended as one of five first-line smoking cessation products. A clinically convenient tool to identify smokers most likely to benefit from NS could assist healthcare practitioners in selecting the optimal treatment for individual patients. OBJECTIVES: To evaluate whether the subjective effects of an initial pre-treatment dose of NS predict 6 month abstinence rates following NS treatment for tobacco dependence. METHODS: One hundred and seventy-five smokers received an initial 1 mg pre-treatment dose of NS and completed a new measure of NS subjective effects (initial spray experience, ISE). This measure, together with demographic and smoking history variables, was examined as a predictor of 6-month point-prevalence (biochemically verified) abstinence rates. RESULTS: Factor analysis revealed positive and negative effects subscales of the ISE. Smokers with higher ratings of positive effects from the pre-treatment NS dose were significantly more likely to be abstinent at 6-month follow-up. These effects were partially mediated by reduction in urge to smoke. CONCLUSIONS: Pending additional validation in human laboratory and clinical studies, assessment of the acute positive subjective effects of initial NS delivery may be an efficient way to predict who will be successful with NS treatment for tobacco dependence.

Administration, Intranasal↗

Predictors of attendance in a randomized clinical trial of nicotine replacement therapy with behavioral counseling.

Participant attendance at smoking cessation-counseling sessions is an important factor in treatment outcome. In this study, we examined the influence of demographic, psychological, and smoking history variables on attendance at a randomized clinical trial comparing transdermal nicotine and nicotine nasal spray that included seven sessions of behavioral group counseling. Of the 353 participants, 70.5% attended all seven sessions. Perfect attendance predicted abstinence from cigarettes at the end of treatment and at 6-month follow-up. In a logistic regression model, higher levels of education and higher body mass index were significant independent predictors of better attendance. There was a significant interaction between type of nicotine replacement (transdermal nicotine vs. nasal spray) and sex: females were less likely than males to have perfect attendance in the nasal spray group, but there was no sex difference in attendance for the transdermal nicotine group. These findings suggest that smokers with lower body mass index and less formal education may benefit from proactive counseling to address individual barriers to attendance at smoking cessation counseling. Additional research in this area would also be valuable to evaluate strategies to promote attendance in these high-risk groups.

Administration, Cutaneous↗

Bilateral prophylactic oophorectomy and ovarian cancer screening following BRCA1/BRCA2 mutation testing.

PURPOSE: Despite the widespread availability of genetic testing for BRCA1/BRCA2 mutations, little is known about the impact of testing on ovarian cancer prevention and screening. For mutation testing to effect cancer mortality, positive test results must be followed by appropriate behavior change. In this study, we prospectively examined the impact of BRCA1/2 testing on the utilization of prophylactic oophorectomy and ovarian cancer screening. PARTICIPANTS AND METHODS: Participants were 289 high-risk women who underwent genetic counseling and testing for alterations in the BRCA1/2 genes. We measured self-reported receipt of bilateral prophylactic oophorectomy (BPO) and utilization of CA-125 and transvaginal ultrasound (TVU) in the year following testing, and examined the impact of test results on these outcomes. In addition, we examined the role of sociodemographic, medical, family history, and psychological variables on the receipt of BPO, CA-125, and TVU. RESULTS: Twenty-seven percent of mutation carriers, 5% of uninformative patients, and 2% of noncarriers received a BPO in the year following testing. In addition to test results, perceived risk for ovarian cancer and family history of ovarian cancer independently predicted receipt of BPO. The receipt of a positive test result was associated with increased utilization of CA-125 and TVU. Additional predictors included perceived risk for ovarian cancer (both CA-125 and TVU) and state anxiety (CA-125). CONCLUSION: These results demonstrate the significant behavioral impact of receiving a positive BRCA1/2 test result. The increased rate of oophorectomy among mutation carriers suggests that testing for BRCA1/2 mutations may ultimately impact ovarian cancer mortality.

Adult↗

Genetic testing for a BRCA1 mutation: prophylactic surgery and screening behavior in women 2 years post testing.

Mutations in the BRCA1 gene are associated with an increased risk of breast and ovarian cancer in carrier women. An understanding of behavioral responses to BRCA1 mutation testing by mutation carriers and non-carriers is important to guide the clinical application of this new technology. This study examined the utilization of genetic testing for a BRCA1 mutation in high-risk individuals and the response of tested women with respect to interventions for early cancer detection and prevention. This study assessed the utilization of genetic testing for both men and women in a large kindred and the behavioral responses by women with respect to use of health care interventions during the 2 years following testing. Participants were offered BRCA1 mutation testing. Surveillance behaviors related to breast and ovarian cancer were assessed by computer-assisted telephone interviews at baseline (prior to genetic counseling and testing), 1-2 weeks, 4-6 months, 1 and 2 years after the provision of test results. Mutation carriers, non-carriers, and individuals of unknown mutation status were compared to determine the impact of test results. Utilization of genetic testing for both men and women are reported and, for women, mammography, breast self-exam, clinical breast exam, mastectomy, oophorectomy, transvaginal ultrasound, and CA125 screening were assessed. Of those fully informed of the opportunity for testing, 55% of the women and 52% of the men pursued genetic testing. With respect to mammography for women 40 years and older, 82% of mutation carriers obtained a mammogram in each year following testing compared to 72% of non-carrier women the first year and 67% the second year. This mammography utilization represents a significant increase over baseline for both mutation carriers and non-carriers. Younger carrier women also significantly increased their mammography utilization from baseline. Overall, 29% of the carrier women did not obtain a single mammogram by 2 years post-testing. At 2 years, 83% of the carrier women and 74% of the non-carriers reported adherence to recommendations for breast self-exam and over 80% of carrier women had obtained a clinical breast examination each year following testing. None of the carrier women had obtained a prophylactic mastectomy by 2 years after testing, although 11% were considering this procedure. Of carrier women 25 years of age and older who had at least one intact ovary at the time of testing, 46% of carriers had obtained an oophorectomy 2 years after testing, including 78% of women 40 years of age and older. The majority of carrier women (73%) had discussed their genetic test results with a medical doctor or health care provider. Our results indicate utilization of genetic testing by a majority of high-risk individuals who received information about testing. Both carriers and non-carriers increased their utilization of mammography and breast self-exam following testing. Oophorectomy was obtained by a large proportion of carrier women in contrast to mastectomy which was not utilized within the first 2 years following testing.

Adult↗

Elucidating the role of genetic factors in smoking behavior and nicotine dependence.

Despite over a decade of intensive tobacco control efforts, a substantial proportion of the world's population continues to smoke. With advances in molecular biology and genomics technology, attention is focusing on the genetic basis of addiction to nicotine. The hope is that by better understanding the biology of nicotine addiction, novel prevention and cessation strategies can be developed and targeted to individuals most likely to benefit. This article provides an overview of currently available data from genetics research on smoking behavior and discusses study design issues to be addressed to make progress in this line of research.

Animals↗

Smoking, alcoholism and genetic polymorphisms alter CYP2B6 levels in human brain.

CYP2B6 metabolizes drugs such as nicotine and bupropion, and many toxins and carcinogens. Nicotine induces CYP2B1 in rat brain and in humans polymorphic variation in CYP2B6 affects smoking cessation rates. The aim of this study was to compare CYP2B6 expression in brains of human smokers and non-smokers and alcoholics and non-alcoholics (n=26). CYP2B6 expression was brain region-specific, and was observed in both neurons and astrocytes. CYP2B6 levels were higher in brains of smokers and alcoholics, particularly in cerebellar Purkinje cells and hippocampal pyramidal neurons, cells known to be damaged in alcoholics. Significantly more (p<0.05) CYP2B6 protein was seen in four brain regions of smoking alcoholics compared to non-smoking non-alcoholics: hippocampus (5.8-fold), caudate nucleus (3.3-fold), putamen (3.0-fold) and cerebellar hemisphere (1.6-fold). The genetic variant C1459T (R487C) has been associated with reduced hepatic enzyme levels, stability and activity. Preliminary genotyping of this small sample (n=24) suggested that individuals with the CC genotype had higher brain CYP2B6 than those with the CT or TT genotype. Higher brain CYP2B6 activity in smokers and alcoholics may cause altered sensitivity to centrally acting drugs, increased susceptibility to neurotoxins and carcinogenic xenobiotics and contribute to central tolerance to nicotine.

Adolescent↗

Effects of dopamine transporter and receptor polymorphisms on smoking cessation in a bupropion clinical trial.

This study examined the role of dopaminergic genes in prospective smoking cessation and response to bupropion treatment in a placebo-controlled clinical trial. Smokers of European ancestry (N=418) provided blood samples for genetic analysis and received either bupropion or placebo (10 weeks) plus counseling. Assessments included the dopamine D2 receptor (DRD2) genotype, dopamine transporter (SLC6A3) genotype, demographic factors, and nicotine dependence. Smoking status was verified at the end of treatment (EOT) and at 6-month follow-up. The results provided evidence for a significant DRD2 * SLC6A3 interaction effect on prolonged smoking abstinence and time to relapse at EOT, independent of treatment condition. Such effects were no longer significant at 6-month follow-up, however. These results provide the first evidence from a prospective clinical trial that genes that alter dopamine function may influence smoking cessation and relapse during the treatment phase.

Bupropion↗

Comparison between two measures of delay discounting in smokers.

Agreement between computer and questionnaire measures of delay discounting in smokers was compared. Correlations between measures for small, medium, or large rewards were significant. Log k values decreased as the reward delay increased, with values lower for the computer task than the questionnaire, with significant differences for small rewards. The 2 measures were related to smoking rate but not to age, gender, or obesity. The Bland-Altman test of agreement indicated large within-subject differences in k values between the 2 measures. The size of the difference between the log k values and magnitude of the log k values were positively related. Results suggest k values from the 2 measures are related but may not be used interchangeably.

Adolescent↗

Intergenerational transmission of tobacco use and dependence: a transdisciplinary perspective.

Numerous questions remain regarding the intergenerational transmission of tobacco use and dependence, and some of these questions are best approached from a transdisciplinary perspective. For example, considering both genetic and environmental influences on cigarette smoking promises to be a fruitful venue for future investigations. In this paper, we consider the evidence regarding intergenerational influences on the transmission of tobacco use and nicotine dependence in both humans and animal models; our focus will be on genetic influences, in utero exposure to nicotine, and some postnatal influences. Research gaps that exist between scientific disciplines are highlighted, and some directions for future research are suggested.

Adult↗

Facilitating transdisciplinary research: the experience of the transdisciplinary tobacco use research centers.

Cigarette smoking is the largest preventable cause of death and morbidity in the United States. Heightened recognition of this public health concern has led researchers from multiple and varied disciplines to address this complex and multidimensional behavior. The need for an alternative research paradigm, focusing on a transdisciplinary approach that integrates work across disciplines in order to advance the field most quickly, has been identified. This recognized need led to the development of the Transdisciplinary Tobacco Use Research Centers (TTURC) initiative, funded jointly by the National Cancer Institute, the National Institute on Drug Abuse, and The Robert Wood Johnson Foundation. This paper discusses the formation and early implementation stages of the initiative, including meetings that led to the development of the TTURCs, funders' and research centers' perspectives on implementation, and early observations about the products of the initiative.

Humans↗

Transdisciplinary science applied to the evaluation of treatments for tobacco use.

Transdisciplinary research involves the integration of measures and methods across diverse response systems and levels of analysis, with that integration occurring via a synthesis of theories and models of different scientific disciplines. This paper first discusses the need for transdisciplinary research. The paper then articulates a model to guide the comprehensive evaluation of treatments for tobacco use and discusses how transdisciplinary research might be integrated into this treatment evaluation model. The potential benefits and costs of a transdisciplinary approach are discussed, along with selected research projects from the Transdisciplinary Tobacco Use Research Centers.

Humans↗

Which adolescents are most receptive to tobacco industry marketing? implications for counter-advertising campaigns.

This study sought to identify adolescents most receptive to tobacco advertising based on individual differences in novelty-seeking personality and other key variables. Confidential self-report surveys were completed by 1,071 high school freshmen at 5 public high schools. The survey included validated measures of novelty-seeking personality, smoking habits, peer and family smoking, and tobacco advertising receptivity. Multiple logistic regression analysis was used to evaluate the independent associations of these variables and demographics with receptivity to tobacco advertising. Of the ninth graders, 44% had moderate to high levels of advertising receptivity and 54% had minimal to low levels of receptivity. Higher levels of receptivity were associated with ever smoking (odds ratio [OR] = 2.59, confidence interval [CI] = 1.99-3.39) and novelty-seeking personality (OR = 2.14, CI = 1.57-2.93). The association of novelty-seeking personality and tobacco advertising receptivity was most pronounced among adolescents who had never had a puff of a cigarette. Counter-advertising messages should consider individual differences in novelty-seeking, because novelty-seekers may be most receptive to tobacco industry promotional campaigns.

Adolescent↗

Individual differences in nicotine intake per cigarette.

The increase in levels of blood nicotine that occurs from smoking a single cigarette, sometimes referred to as a "nicotine boost," is an individualized measure of how much nicotine has been extracted from smoking a cigarette. This study investigated the demographic, smoking status, and psychological predictors of nicotine boost in a sample of 190 treatment-seeking smokers. Boost was assessed by comparing plasma nicotine levels before and after participants smoked one of their own brand cigarettes ad libitum. Positive affect (mood) was a significant positive predictor of nicotine boost, controlling for baseline cotinine levels and cigarette brand (Federal Trade Commission) nicotine delivery. However the proportion of variability accounted for in the model was relatively small (5%). Future research on individual differences in nicotine boost is warranted to clarify the role of psychological, physiological, and cigarette-related determinants.

Adolescent↗

Applying genetic approaches to the treatment of nicotine dependence.

To advance the science of tobacco control, an enhanced understanding of the bio-behavioral basis of nicotine addiction is needed. In this study, we provide an overview of data from investigations of genetic factors in smoking behavior, discuss potential bio-behavioral mechanisms and effect modifiers, and suggest avenues for pharmacogenetics research in the area of smoking cessation treatment. The evidence to date is very consistent with respect to the significance of genetic contributions to smoking behavior. However, attempts to elucidate the role of specific genetic variants have met with mixed success. Explanations for the lack of consistency in the results of genetic association studies include biases in ascertainment, ethnic admixture, lack of attention to co-variates or modifiers of genetic risk, and the need for more refined phenotypes. As the field of genetics and smoking research progresses, increasing attention is being devoted to gene-environment interactions, with particular attention to the identification of genetic variants that may modify the effects of pharmacological treatment for smoking. With advances in molecular biology and genomics technology, individualized tailoring of smoking cessation therapy to genotype is within our grasp. Such research has the potential to improve treatment outcome, thereby reducing morbidity and mortality from smoking-related disease.

Behavior Therapy↗

Mediating mechanisms for the impact of bupropion in smoking cessation treatment.

Several studies have documented the effectiveness of bupropion for smoking cessation, yet little is known about the mechanisms by which it facilitates abstinence. In this placebo-controlled randomized trial. We examined whether bupropion's effects on cessation were mediated by changes in withdrawal and/or negative or positive affect (PA). Two hundred and fifty-one smokers received 10-week treatment with bupropion or placebo, plus behavioral counseling. Changes in affect and withdrawal symptoms from pre-quit to 1 week post quit were examined as mediating variables in structural equation models. Cotinine-verified 7-day point prevalence cessation rates at the end of treatment (8-weeks post quit date) were 48% for bupropion and 29% for placebo (P=0.001). There were significant treatment effects on withdrawal and negative affect (NA); however, only change in NA predicted cessation. In a path model, change in NA was a significant mediator of bupropion's effects on cessation. However, the proportion of variance accounted for by this mediator was small, suggesting that other unmeasured factors play an important role. Laboratory-based paradigms may be useful to identify other mediators of bupropion's effects, thereby pointing to mechanisms of effect that can be bolstered in future treatment studies.

Adult↗

BRCAPRO validation, sensitivity of genetic testing of BRCA1/BRCA2, and prevalence of other breast cancer susceptibility genes.

PURPOSE: To compare genetic test results for deleterious mutations of BRCA1 and BRCA2 with estimated probabilities of carrying such mutations; to assess sensitivity of genetic testing; and to assess the relevance of other susceptibility genes in familial breast and ovarian cancer. PATIENTS AND METHODS: Data analyzed were from six high-risk genetic counseling clinics and concern individuals from families for which at least one member was tested for mutations at BRCA1 and BRCA2. Predictions of genetic predisposition to breast and ovarian cancer for 301 individuals were made using BRCAPRO, a statistical model and software using Mendelian genetics and Bayesian updating. Model predictions were compared with the results of genetic testing. RESULTS: Among the test individuals, 126 were Ashkenazi Jewish, three were male subjects, 243 had breast cancer, 49 had ovarian cancer, 34 were unaffected, and 139 tested positive for BRCA1 mutations and 29 for BRCA2 mutations. BRCAPRO performed well: for the 150 probands with the smallest BRCAPRO carrier probabilities (average, 29.0%), the proportion testing positive was 32.7%; for the 151 probands with the largest carrier probabilities (average, 95.2%), 78.8% tested positive. Genetic testing sensitivity was estimated to be at least 85%, with false-negatives including mutations of susceptibility genes heretofore unknown. CONCLUSION: BRCAPRO is an accurate counseling tool for determining the probability of carrying mutations of BRCA1 and BRCA2. Genetic testing for BRCA1 and BRCA2 is highly sensitive, missing an estimated 15% of mutations. In the populations studied, breast cancer susceptibility genes other than BRCA1 and BRCA2 either do not exist, are rare, or are associated with low disease penetrance.

Adult↗

All in the family: evaluation of the process and content of sisters' communication about BRCA1 and BRCA2 genetic test results.

Despite the potential importance of family communication, little is known about the process and content of communicating BRCA1/2 test results to relatives. The objectives of this observational study were to describe the process and content of communicating BRCA1/2 test results to sisters, and to evaluate whether the proband's carrier status influenced communication outcomes. Participants were 43 women who were the first family member to have genetic testing (probands). Probands reported on communication outcomes for 81 sisters. Process and content variables were evaluated 1-month after receipt of BRCA1/2 test results using the Family Communication Questionnaire (FCQ). Overall, BRCA1/2 test results were communicated to 85% of sisters, and carriers communicated their results to significantly more sisters compared to uninformative (96% vs. 76%, FET = 0.02). The most important reason for communicating results was to provide genetic risk information; however, compared to uninformatives, carriers communicated their results to significantly more sisters to obtain emotional support (74%) and to get advice about medical decisions (42%) (FET = 0.001). Carriers also discussed the possibility of discrimination and recommendations for cancer management with significantly more sisters. Among sisters to whom BRCA1/2 test results were not communicated, the most important reason for not sharing test results was because of emotionally distant relationships. The results of this study suggest that probands are likely to quickly communicate their BRCA1/2 test results to relatives and that although needs for social support may motivate family communication, emotionally distant relationships may be a barrier to communication with relatives.

Adult↗