Christopher Jepson

Psychological side effects of breast cancer screening.

Evaluated the impact of receiving abnormal mammogram results on womens anxiety and breast cancer worries and on their breast self-examination (BSE) frequency and intentions to obtain subsequent mammograms. A telephone survey was conducted with 308 women 50 years old and older approximately 3 months following a screening mammogram. Subjects included women with suspicious abnormal mammograms, nonsuspicious abnormal mammograms, and normal mammograms. Women with suspicious abnormal mammograms exhibited significantly elevated levels of mammography-related anxiety and breast cancer worries that interfered with their moods and functioning, despite the fact that diagnostic work-ups had ruled out breast cancer. Women with moderate levels of impairment in mood or functioning were more likely to practice monthly BSE than women with either high or low levels of impairment. Breast cancer worries, perceived susceptibility to breast cancer, and physician encouragement to get mammograms all exhibited independent positive relationships to mammogram intentions.

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.

ADVANCING GERIATRIC NURSING PRACTICE; A Specialized Home Care Intervention Improves Survival Among Older Post-Surgical Cancer Patients

CONTEXT: Changes in the healthcare system have resulted in shortened hospital stays, moving the focus of care from the hospital to the home. Patients are discharged post‐operatively with ongoing needs, and whether they receive nursing care post‐hospitalization can influence their recovery and survival. Little information is available about the factors that influence outcomes, including the survival of older cancer patients after cancer surgery.

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.

Varenicline Improves Mood and Cognition during Smoking Abstinence

BACKGROUND Neuronal nicotinic acetylcholine receptors (nAChRs) are a key target in medication development for various neuropsychiatric disorders, including nicotine dependence. Varenicline, a partial agonist at the alpha4beta2 nAChRs, is a new, efficacious medication for nicotine dependence. Its effects on the affective and cognitive dimensions of nicotine withdrawal have yet to be well characterized. METHODS Sixty-seven treatment-seeking smokers were administered varenicline (x 21 days) and placebo (x 21 days) in a double-blind within-subject crossover design. Following medication run-up (Days 1-10), there was a 3-day mandatory smoking abstinence phase (Days 11-13) during which subjective symptoms and cognitive performance were assessed. Participants were reexposed to a scheduled smoking lapse (Day 14) and followed for days to lapse (Days 15-21) in each medication period. RESULTS In the varenicline period, compared with placebo, withdrawal symptoms (p = .04), smoking urges (p < .001), and negative affect (p = .01) during manditory abstinence were significantly lower, and levels of positive affect (p = .046), sustained attention (p = .018), and working memory (p = .001) were significantly greater. Varenicline also significantly reduced subjective rewarding effects of the scheduled smoking lapse (e.g., satisfaction, relief, liking; p = .003). Medication effects on days to lapse following the scheduled smoking lapse were dependent on treatment order (p = .001); among participants who received placebo in the first period, varenicline increased days of abstinence in the follow-up period. CONCLUSIONS These data identify novel affective and cognitive effects of varenicline and may have implications for medication development for other neuropsychiatric conditions.

Impact of CYP2A6 genotype on pretreatment smoking behaviour and nicotine levels from and usage of nicotine replacement therapy

We investigated the effect of slow metabolism of nicotine, predicted by CYP2A6 genotypes resulting in ⩽50% activity, on baseline smoking behaviours and treatment variables in an open-label nicotine replacement therapy (NRT) clinical trial. Caucasian smokers with CYP2A6 slow vs normal metabolism had lower metabolic activity, indicated by the 3-hydroxycotinine/cotinine ratio (0.23±0.17 vs 0.45±0.22, P<0.01, respectively). CYP2A6 slow metabolizers also smoked fewer cigarettes per day compared to normal metabolizers (20±7 vs 24±10, respectively, P<0.04). With nicotine patch use, slow metabolizers had higher nicotine plasma levels compared to normal metabolizers (22.8±4.6 vs 15.8±7.6 ng/ml, respectively, P=0.02) while using the same numbers of patches/week. With nicotine spray use, where like in smoking the nicotine intake can be easily adjusted to adapt to rates of metabolism, slow metabolizers achieved similar nicotine levels compared to normal metabolizers (5.8±4.1 vs 8.0±9.1 ng/ml, P=0.82), by using fewer doses of nicotine spray/day (4.8±3.6 vs 10.5±8.0, respectively, P<0.02). These findings indicate that CYP2A6 genotype influences smoking behaviour in a Caucasian treatment-seeking population and that CYP2A6 genotype affects plasma levels obtained from, and usage of, NRT.

The Inclusion of Patient Testimonials in Decision Aids Effects on Treatment Choices

Background. Decision aids often provide statistical information and patient testimonials to guide treatment choices. This raises the possibility that the testimonials will overwhelm the statistical information. Methods. Prospective jurors in Philadelphia County were presented with hypothetical statistical information about the percentage of angina patients who benefit from angioplasty and bypass surgery (50% and 75%, respectively). They were also given written testimonials from hypothetical patients who had benefited or not benefited from each of the two treatments. The numbers of patients benefiting and not benefiting were varied to be either proportionate to the statistical information or disproportionate. In study 1, all participants received 1 testimonial from a patient who had benefited from angioplasty and 1 from a patient who had not. Participants receiving the proportionate questionnaire version were also given 3 testimonials from patients who benefited from bypass surgery and 1 from a patient who did not, coinciding with the hypothetical statistical information. In contrast, participants receiving the disproportionate questionnaire version received only 1 testimonial from a patient who benefited from surgery and 1 from a patient who did not. In study 2, all participants received 2 examples of patients who benefited from angioplasty and 2 who did not. Participants with the proportionate questionnaire version received the same testimonials regarding surgery as in study 1. Those receiving the disproportionate questionnaire version received 2 testimonials from patients who benefited from bypass and 2 from patients who did not. Finally, a separate set of participants in study 2 received a questionnaire with no testimonials. Results. In study 1, 30% of participants receiving the disproportionate questionnaire version chose bypass surgery versus 44% of those receiving the proportionate questionnaire (P = 0.002 by X2). In study 2, 34% of participants receiving the disproportionate questionnaire version chose bypass surgery versus 37% of those receiving the proportionate questionnaire (P= 0.59 by X2). Of those receiving no patient testimonials, 58% chose bypass surgery. Conclusions. The inclusion of written patient testimonials significantly influenced hypothetical treatment choices. Efforts to make the mix of positive versus negative testimonials proportionate to statistical information may, under some circumstances, affect choices in ways that cannot automatically be assumed to be optimal.

Working memory deficits predict short-term smoking resumption following brief abstinence.

As many as one-half of smokers relapse in the first week following a quit attempt, and subjective reports of cognitive deficits in early abstinence are associated with increased relapse risk. This study examined whether objective cognitive performance after 3 days of abstinence predicts smoking resumption in a 7-day simulated quit attempt. Sixty-seven treatment-seeking smokers received either varenicline or placebo (randomized double-blind) for 21 days. Following medication run-up (days 1-10), there was a 3-day mandatory (biochemically confirmed) abstinence period (days 11-13) during which working memory (Letter-N-Back Task) and sustained attention (Continuous Performance Task) were assessed (day 13). Participants were then exposed to a scheduled smoking lapse and instructed to try to remain abstinent for the next 7 days (days 15-21). Poorer cognitive performance (slower correct reaction time on Letter-N-Back task) during abstinence predicted more rapid smoking resumption among those receiving placebo (p=0.038) but not among those receiving varenicline. These data lend further support for the growing recognition that cognitive deficits involving working memory are a core symptom of nicotine withdrawal and a potential target for the development of pharmacological and behavioral treatments.

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.

Do Nonpatients Underestimate the Quality of Life Associated with Chronic Health Conditions because of a Focusing Illusion

Background. A number of studies show that the general public often estimates that the quality of life (QOL) associated with various health conditions is worse than patients say it is. These studies raise the possibility that people overestimate the impact that unfamiliar health conditions will have on their quality of life. One possible reason people overestimate this is because they are susceptible to a focusing illusion—when asked to imagine themselves in unfamiliar circumstances, people overestimate the emotional impact of those features of their life that would change. Methods. The authors surveyed members of the general public to test the hypothesis that their QOL ratings of hypothetical health conditions would be higher (indicating a better quality of life) after thinking about how the health condition would affect a broad range of life domains. Across 3 experiments, the authors varied the health conditions people were asked to consider (either paraplegia, below-the-knee amputation, or partial blindness), the life domains they were asked to consider, the response mode with which they evaluated how each health condition would affect each life domain, whether subjects rated the health condition before and after considering life domains or only after, and whether subjects rated their own current quality of life first. Results. Across 3 experiments, using 10 different questionnaire versions, only 1 instance was found in which subjects’ ratings were significantly higher after thinking about the effect of the health condition on life domains than before, and the magnitude of this increase was small. Conclusion. It could not be established that a focusing illusion contributes significantly to the discrepancy in QOL ratings of patients and nonpatients. Further research should explore other factors that could contribute to the discrepancy or other ways of testing for the influence of a focusing illusion.