Biomedical subjects

Christopher Jepson

Publications and source records attributed to Christopher Jepson.

At least 19 recordsLinked to original sources

PubMed2007

CYP2B6 genotype alters abstinence rates in a bupropion smoking cessation trial.

BACKGROUND: CYP2B6 is the primary enzyme involved in bupropion (Zyban; GlaxoSmithKline, Research Triangle Park, North Carolina) metabolism. Genetic polymorphisms in CYP2B6, such as CYP2B6*6, can alter bupropion metabolism and may affect bupropion treatment outcome. METHODS: Subjects participated in a smoking cessation clinical trial of bupropion versus placebo. The main outcome was a 7-day point prevalence abstinence rate measured 10 weeks after the start of treatment (i.e., end of treatment) and at the 6-month follow-up; secondary outcomes were severity of adverse effects, withdrawal, and urge to smoke. Subjects were haplotyped for the CYP2B6*6 variants. RESULTS: Among smokers in the CYP2B6*6 group (CYP2B6*1/*6 or CYP2B6*6/*6 genotype, n = 147, 45% of the population), bupropion produced significantly higher abstinence rates than placebo at the end of treatment (32.5% vs. 14.3%, p = .01) and at the 6-month follow-up (31.2% vs. 12.9%, p = .008). In contrast, bupropion was no more effective than placebo for smokers in the CYP2B6*1 group (CYP2B6*1/*1, n = 179) at the end of treatment (31.0% vs. 31.6%, p = .93) or at the 6-month follow-up (22.0% vs. 21.5%, p = .94). There was a significant genotype by treatment interaction at the end of treatment (odds ratio [OR] = 2.97, confidence interval [CI] = 1.05-8.40, p = .04), which was similar at 6-month follow-up (OR = 2.98, CI = .98-9.06, p = .05). CONCLUSIONS: These data suggest that smokers with the CYP2B6*6 genotype have a higher liability to relapse on placebo and that they may be good candidates for bupropion treatment for smoking cessation.

Adult↗

PubMed2006

Role of functional genetic variation in the dopamine D2 receptor (DRD2) in response to bupropion and nicotine replacement therapy for tobacco dependence: results of two randomized clinical trials.

Although bupropion and nicotine replacement therapy (NRT) are efficacious tobacco dependence treatments, there is substantial interindividual variability in therapeutic response and most smokers relapse. Pharmacogenetics research may improve treatment outcomes by identifying genetic variants predictive of therapeutic response. We investigated the roles of two functional genetic variants in the dopamine D2 receptor (DRD2) gene in response to pharmacotherapy for tobacco dependence among participants in two randomized clinical trials with a 6-month follow-up period: a double-blind placebo-controlled trial of bupropion (n=414) and an open label trial of transdermal nicotine vs nicotine nasal spray (n=368). At the end of the treatment phase, a statistically significant (p=0.01) interaction between the DRD2 - 141C Ins/Del genotype and treatment indicated a more favorable response to bupropion among smokers homozygous for the Ins C allele compared to those carrying a Del C allele. By contrast, smokers carrying the Del C allele had statistically significantly (p=0.006) higher quit rates on NRT compared to those homozygous for the Ins C allele, independent of NRT type. The C957T variant was also associated (p=0.03) with abstinence following NRT. These results suggest that bupropion may be the preferred pharmacologic treatment for smokers homozygous for the DRD2 - 141 Ins C allele, while NRT may be more beneficial for those who carry the Del C allele. Study findings require confirmation in additional larger samples before they are applied in practice.

Administration, Intranasal↗

PubMed2005

Naltrexone reduces the relative reinforcing value of nicotine in a cigarette smoking choice paradigm.

RATIONALE: Human behavioral pharmacology studies can examine how medications that target different neurotransmitter systems influence different aspects of smoking. Naltrexone and bupropion have been shown to alter ad lib smoking behavior; however, medication effects on nicotine reward in a cigarette choice paradigm have yet to be investigated. OBJECTIVE: This study explored the effects of an acute dose of naltrexone, bupropion, or placebo on the relative reinforcing value of nicotine from cigarette smoking using new nicotine and de-nicotinized (Quest, 0.6 and 0.05 mg = "denicotinized") cigarettes. METHODS: In a double-blind, within-subjects design, 26 dependent smokers participated in three experimental cigarette smoking sessions following pretreatment with either naltrexone (50 mg), bupropion (300 mg), or placebo. After medication administration and 2 h of monitored deprivation from cigarettes and food, participants rated their responses to the initial exposure to the cigarettes and then participated in four choice sessions over a 2-h period during which they could take four puffs from either cigarette. RESULTS: The relative reinforcing value of nicotine, as measured by the number of nicotine puffs chosen out of 16, was significantly lower following naltrexone compared to placebo. There were no effects of an acute dose of bupropion on nicotine choices. CONCLUSIONS: These results suggest that naltrexone may reduce the relative reinforcing effects of nicotine via cigarette smoking and support ongoing investigation of opioid antagonists as potential smoking cessation pharmacotherapies.

Adolescent↗

PubMed2005

Effects of different nicotine replacement therapies on postcessation psychological responses.

Transdermal nicotine patch (TN) and nicotine nasal spray (NS) are both efficacious forms of smoking cessation treatment, but have different pharmacokinetic properties and modes of action. To understand better psychological responses to treatment, we investigated the effects of TN versus NS on positive affect, negative affect, and withdrawal symptoms during treatment. Participants were randomly assigned to receive TN (n=172) or NS (n=163) plus seven sessions of behavioral counseling, and completed self-report questionnaires at pretreatment and during treatment. TN participants, but not NS participants, reported significant increases in positive affect during treatment. Increases in negative affect and withdrawal were observed, independent of treatment. Only changes in negative affect predicted relapse by the end of the treatment phase. These findings indicate that, although TN may enhance positive affect for smokers in treatment compared with NS, only changes in negative affect predict treatment outcome.

Administration, Cutaneous↗

PubMed2005

In a mailed physician survey, questionnaire length had a threshold effect on response rate.

OBJECTIVE: To examine the association between questionnaire length and response rate in a mailed survey of generalist physicians randomly selected from the American Medical Association master file. STUDY DESIGN AND SETTING: In a pilot study, otherwise similar questionnaires of 30 different lengths (849 to 1,867 words) were mailed to 192 physicians in April 1999. In the main study, questionnaires of 16 different lengths (564 to 988 words) were mailed to 1,700 physicians between June 1999 and January 2000. RESULTS: In the pilot study, response rate decreased from 60% for questionnaires 849 words in length to 16.7% for questionnaires over 1,800 words in length. Logistic regression revealed an odds ratio of 0.887 (95%CI 0.813, 0.968; p=0.006) for word count, expressed in units of 100 words. In the main study, response rate varied between 51.5% and 71.4%. Logistic regression showed no association between response and word count (OR 0.988; 95%CI 0.896, 1.090; p=0.81). CONCLUSION: There appears to have been a threshold in these studies of approximately 1,000 words. Questionnaires above the threshold had lower response rates than those below it (38.0% vs. 59.4%).

Health Care Surveys↗

PubMed2005

Increases in hyperactive-impulsive symptoms predict relapse among smokers in nicotine replacement therapy.

Inattention and hyperactive-impulsive symptoms have been associated with nicotine dependence. In an open-label randomized trial (N = 454) of transdermal nicotine versus nicotine nasal spray, we examined whether increases in inattention and hyperactive-impulsive symptoms measured by self-report in the first quit week predicted relapse at the end of 8 weeks of treatment (EOT). During the first quit week, 166 (37%) participants reported an increase whereas 288 (63%) reported no change/decrease in total symptoms; changes were not influenced by treatment type. In a logistic regression model of abstinence, an increase in total symptoms in the first quit week significantly reduced odds of abstinence at EOT (continuous change score: OR = 0.94, 95% CI = 0.91-0.98, p = .002; dichotomized change score: OR = 0.57, 95% CI = 0.37-0.87, p = .009). Early increases in inattention and hyperactive-impulsive symptoms following quit date during nicotine replacement therapy predicted relapse to smoking, suggesting that treatments targeting these symptoms in the first quit week may facilitate abstinence.

Adult↗

PubMed2005

Ignorance of hedonic adaptation to hemodialysis: a study using ecological momentary assessment.

Healthy people generally underestimate the self-reported well-being of people with disabilities and serious illnesses. The cause of this discrepancy is in dispute, and the present study provides evidence for 2 causes. First, healthy people fail to anticipate hedonic adaptation to poor health. Using an ecological momentary assessment measure of mood, the authors failed to find evidence that hemodialysis patients are less happy than healthy nonpatients are, suggesting that they have largely, if not completely, adapted to their condition. In a forecasting task, healthy people failed to anticipate this adaptation. Second, although controls understated their own mood in both an estimation task and a recall task, patients were quite accurate in both tasks. This relative negativity in controls' estimates of their own moods could also contribute to their underestimation of the moods and overall well-being of patients.

Adaptation, Psychological↗

PubMed2005

Disability and sunshine: can hedonic predictions be improved by drawing attention to focusing illusions or emotional adaptation?

People frequently mispredict the long-term emotional impact of circumstances. The authors examine 2 causes of such mispredictions-a focusing illusion and underappreciation of adaptation. In Experiment 1, the authors found, in 852 adults, that quality of life estimates (for living with disability) were not increased by reducing focusing illusions. In Experiment 2, the authors found, in 698 adults, that people's disability estimates were increased by asking them to reflect on adaptation. In Experiment 3, the authors found, across 312 Midwestern college students, that both approaches reduced the participants' predictions of the life satisfaction of their peers living in southern California. In the case of living in a better climate, the results suggest that attention to either cause influences people's predictions, whereas in the case of chronic disability, the results suggest that it is easier to get people to appreciate adaptation than it is to reduce focusing illusions.

Adaptation, Psychological↗

PubMed2005

Association of catechol-O-methyltransferase with smoking cessation in two independent studies of women.

OBJECTIVES AND METHODS: The Val108/158Met polymorphism in the gene that encodes COMT, a dopamine metabolizing enzyme, results in a three- to four-fold reduction in COMT activity. To determine if the lower activity Met allele of COMT was associated with smoking cessation in women, we used two independent studies: a population-based case--control study and a nicotine replacement clinical trial. RESULTS: In the case--control study, women with two Met alleles were significantly more likely to be ex-smokers than current smokers [OR=1.82, 95% CI (1.05, 3.17), P=0.03]. In the nicotine replacement clinical trial, among women, the Met/Met genotype was associated with a higher probability of smoking cessation based on both point prevalence and prolonged abstinence outcomes [OR=2.96, 95% CI (1.07, 8.14), P=0.04; OR=3.23, 95% CI (1.13, 9.20), P=0.03, respectively]. CONCLUSIONS: This first report of a significant association between COMT Val108/158Met and smoking cessation suggests that COMT variation has an effect on smoking behavior in women.

Aged↗

PubMed2003

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↗

PubMed2003

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↗

PubMed2003

The influence of cost-effectiveness information on physicians' cancer screening recommendations.

Physicians are increasingly faced with choices in which one screening strategy is both more effective and more expensive than another. One way to make such choices is to examine the cost-effectiveness of the more costly strategy over the less costly one. However, little is known about how cost-effectiveness information influences physicians' screening decisions. We surveyed 900 primary care US physicians, and presented each with a hypothetical cancer-screening scenario. We created three familiar screening scenarios, involving cervical, colon, and breast cancer. We also created three unfamiliar screening scenarios. Physicians were randomized to receive one of nine questionnaires, each containing one screening scenario. Three questionnaires posed one of the familiar screening scenarios without cost-effectiveness information, three posed one of the familiar scenarios with cost-effectiveness information, and three posed one of the unfamiliar scenarios with cost-effectiveness information. The cost-effectiveness information for familiar scenarios was drawn from the medical literature. The cost-effectiveness information for unfamiliar scenarios was fabricated to match that of a corresponding familiar scenario. In all questionnaires, physicians were asked what screening alternative they would recommend. A total of 560 physicians responded (65%). For familiar scenarios, providing cost-effectiveness information had at most a small influence on physicians' screening recommendations; it reduced the proportion of physicians recommending annual Pap smears (p=0.003), but did not significantly alter the aggressiveness of colon cancer and breast cancer screening (both p's<0.1). For all three unfamiliar scenarios, physicians were significantly less likely to recommend expensive screening strategies than in corresponding familiar scenarios (all p's<0.001). Physicians' written explanations revealed a number of factors that moderated the influence of cost-effectiveness information on their screening recommendations. Providing physicians with cost-effectiveness information had only a moderate influence on their screening recommendations for cervical, colon, and breast cancer. Significantly, fewer physicians recommended aggressive screening for unfamiliar cancers than for familiar ones, despite similar cost-effectiveness. Physicians are relatively reluctant to abandon common screening strategies, even when they learn that they are expensive, and are hesitant to adopt unfamiliar screening strategies, even when they learn that they are inexpensive.

Adult↗

PubMed2003

Whose quality of life? A commentary exploring discrepancies between health state evaluations of patients and the general public.

There is often a discrepancy between quality of life estimates from patients and the general public. These discrepancies are of concern to the disability community, who worry that the public does not understand how valuable life can be for people with disabilities; policy planners, who must decide whose quality of life estimates to use in economic analysis; and practitioners and patients facing difficult medical decisions, who may have to worry that people have difficulty imagining unfamiliar health states. We outline several factors that may contribute to these discrepancies. Discrepancies might occur because patients and the public interpret health state descriptions differently--for example, making different assumptions about the recency of onset of the health state, or about the presence of comorbidities. Discrepancies might also arise if patients adapt to illness and the public does not predict this adaptation; because of response shift in how people use quality of life scales; because of a focusing illusion whereby people forget to consider obvious aspects of unfamiliar health states; because of contrast effects, whereby negative life events make people less bothered by less severe negative life events; and because of different vantage points, with patients viewing their illness in terms of the benefits that would result from regaining health, while the public views the illness in terms of the costs associated with losing good health. Decisions about whose values to measure for the purposes of economic analyses, and how to measure discrepancies, should take these potential contributing factors into account.

Adaptation, Psychological↗

PubMed2003

Don't ask, don't tell: a change in medical student attitudes after obstetrics/gynecology clerkships toward seeking consent for pelvic examinations on an anesthetized patient.

OBJECTIVE: We explore whether the completion of an obstetrics/gynecology clerkship is associated with a decline in the importance that students place on seeking permission from the patient before conducting a pelvic examination while she is anesthetized. STUDY DESIGN: Students at five Philadelphia area medical schools (n = 401 students) were asked how important it would be for a patient to be told that a medical student will perform a pelvic examination while she is anesthetized. We examined associations between the completion of an obstetrics/gynecology clerkship and attitudes toward consent with the use of linear regression to adjust for gender and the total amount of clerkship experience. RESULTS: After the data were controlled for gender and the total number of clerkships that had been completed, we found that students who had completed an obstetrics/gynecology clerkship thought that consent was significantly less important than did those students who had not completed a clerkship (P =.01). CONCLUSION: To avoid this decline in attitudes toward seeking consent, clerkship directors should ensure that students perform examinations only after patients have given consent explicitly.

Anesthesia, General↗

PubMed2003

Incremental and average cost-effectiveness ratios: will physicians make a distinction?

Physicians are increasingly asked to use cost-effectiveness information when evaluating alternative health care interventions. Little is known about how the way such information is presented can influence medical decision making. We presented physicians with hypothetical screening scenarios with multiple options, varying the type of cost-effectiveness ratios provided as well as whether the scenarios described cancer screening settings that were familiar or unfamiliar. Half the scenarios used average cost-effectiveness ratios, as commonly reported, calculating benefits and costs relative to a no-screening option. The other half used the preferred incremental cost-effectiveness ratios, with each option's benefits and costs calculated relative to the next best alternative. Relative to average cost-effectiveness ratios, incremental cost-effectiveness information significantly reduced preference for the most expensive screening strategies in two of three unfamiliar scenarios. No such difference was found for familiar scenarios, for which physicians likely have established practice patterns. These results suggest that, in unfamiliar settings, average cost-effectiveness ratios as reported in many analyses reported in the literature can hide the often high price for achieving incremental health care goals, potentially causing physicians to choose interventions with poor cost effectiveness.

Cost-Benefit Analysis↗

PubMed2003

Misperceptions about beta-blockers and diuretics: a national survey of primary care physicians.

BACKGROUND: Based on a series of clinical trials showing no difference in the effectiveness or tolerability of most major classes of antihypertensive medications, the Joint National Commission on High Blood Pressure Treatment recommends that physicians prescribe beta-blockers or diuretics as initial hypertensive therapy unless there are compelling indications for another type of medication. Nevertheless, many physicians continue to favor more expensive medications like angiotensin-converting enzyme (ACE) inhibitors and calcium channel blockers as first line agents. The persistent use of these agents raises questions as to whether physicians perceive ACE inhibitors and calcium channel blockers to be better than beta-blockers and diuretics. METHODS: We surveyed 1,200 primary care physicians in 1997, and another 500 primary care physicians in 2000, and asked them to estimate the relative effectiveness and side effects of 4 classes of medication in treating a hypothetical patient with uncomplicated hypertension: ACE inhibitors, beta-blockers, calcium channel blockers, and diuretics. In addition, we asked them to indicate whether they ever provided free samples of hypertension medications to their patients. RESULTS: Perceptions of the relative effectiveness and side effects of the 4 classes of hypertension medications did not significantly change over the 3 years, nor did prescription recommendations. Physicians perceive that diuretics are less effective at lowering blood pressure than the other 3 classes (P <.001). They also perceive that beta-blockers are less tolerated than the other 3 classes (P <.001). In a multivariate model, perceptions of effectiveness and tolerability displayed significant associations with prescription preference independent of background variables. The only other variable to contribute significantly to the model was provision of free medication samples to patients. CONCLUSIONS: Despite numerous clinical trials showing no difference in the effectiveness or side-effect profiles of these 4 classes of drugs, most physicians believed that diuretics were less effective and beta-blockers were less tolerated than other medications. Moreover, their prescription practices were associated with their provision of free samples provided by pharmaceutical representatives, even after adjusting for other demographic characteristics. Efforts to increase physicians' prescribing of beta-blockers and diuretics may need to be directed at overcoming misunderstandings about the effectiveness and tolerability of these medicines.

Adrenergic beta-Antagonists↗

PubMed2003

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↗

PubMed2003

When money is saved by reducing healthcare costs, where do US primary care physicians think the money goes?

BACKGROUND: Physician willingness to reduce medical costs is mixed. Some physicians might be unwilling to reduce medical costs because they are concerned about where the savings would go. OBJECTIVE: To determine whether primary care physicians might be less willing to choose a less expensive, less effective cancer screening alternative if they believe that the money saved goes to insurance companies. DESIGN: Anonymous mailed survey. PARTICIPANTS: A total of 865 US primary care physicians. MAIN OUTCOME MEASURES: Responses to one of several clinical vignettes presenting a choice between a less expensive, less effective cancer screening option and a more expensive, more effective alternative and responses to where physicians thought the savings might go if they chose the cheaper alternative. RESULTS: Fifty-three percent of physicians chose the most expensive screening alternative. In aggregate, physicians responded that more of any money saved would go to the managers or owners of insurance companies than to increased clinical services or reduced insurance premiums. Physicians choosing the more expensive screening test were more likely to believe that money saved from choosing the less expensive test would go to insurance company profits and salaries rather than to increased clinical services or reduced premiums (P < .001). CONCLUSIONS: Although US primary care physicians vary in where they think money saved in healthcare goes, most believe that more of it goes to the salaries of insurance company executives and the profits of insurance company owners than to improved clinical services or reduced premiums. The more physicians believe that this is where the money goes, the less willing they are to reduce healthcare costs.

Attitude of Health Personnel↗