An analysis of fosaprepitant-induced venous toxicity in patients receiving highly emetogenic chemotherapy.

PURPOSE: Fosaprepitant is an antiemetic used for chemotherapy-induced nausea and vomiting. We recently reported increased infusion site adverse events (ISAE) in a cohort of breast cancer patients receiving chemotherapy with doxorubicin and cyclophosphamide (AC). In this current study, we evaluated the venous toxicity of fosaprepitant use with non-anthracycline platinum-based antineoplastic regimens. METHODS: A retrospective review was conducted of the first 81 patients initiated on fosaprepitant among patients receiving highly emetogenic chemotherapy, on or after January 1, 2011 at Mayo Clinic Rochester. None of these regimens included an anthracycline. Data collected included baseline demographics, chemotherapy regimen, type of intravenous access and type, and severity of ISAE. Data from these patients were compared to previously collected data from patients who had received AC. Statistical analysis using χ 2 and univariate logistic regression was used to evaluate the association between treatment regimen, fosaprepitant, and risk of ISAE. RESULTS: Among these 81 patients, the incidence of ISAE was 7.4% in the non-anthracycline platinum group. The most commonly reported ISAE were swelling (3%), extravasation (3%), and phlebitis (3%). When stratified by regimen, fosaprepitant was associated with a statistically significant increased risk of ISAE in the anthracycline group (OR 8.1; 95% CI 2.0-31.9) compared to the platinum group. CONCLUSIONS: Fosaprepitant antiemetic therapy causes significant ISAE that are appreciably higher than previous reports. Patients receiving platinum-based chemotherapy appear to have less significant ISAE than do patients who receive anthracycline-based regimens.

Genetic susceptibility loci, environmental exposures, and Parkinson's disease: a case-control study of gene-environment interactions.

BACKGROUND: Prior studies causally linked mutations in SNCA, MAPT, and LRRK2 genes with familial Parkinsonism. Genome-wide association studies have demonstrated association of single nucleotide polymorphisms (SNPs) in those three genes with sporadic Parkinson's disease (PD) susceptibility worldwide. Here we investigated the interactions between SNPs in those three susceptibility genes and environmental exposures (pesticides application, tobacco smoking, coffee drinking, and alcohol drinking) also associated with PD susceptibility. METHODS: Pairwise interactions between environmental exposures and 18 variants (16 SNPs and two variable number tandem repeats, or "VNTRs") in SNCA, MAPT and LRRK2, were investigated using data from 1098 PD cases from the upper Midwest, USA and 1098 matched controls. Environmental exposures were assessed using a validated telephone interview script. RESULTS: Five pairwise interactions had uncorrected P-values < 0.05. These included pairings of pesticides × SNCA rs3775423 or MAPT rs4792891, coffee drinking × MAPT H1/H2 haplotype or MAPT rs16940806, and alcohol drinking × MAPT rs2435211. None of these interactions remained significant after Bonferroni correction. Secondary analyses in strata defined by type of control (sibling or unrelated), sex, or age at onset of the case also did not identify significant interactions after Bonferroni correction. CONCLUSIONS: This study documented limited pairwise interactions between established genetic and environmental risk factors for PD; however, the associations were not significant after correction for multiple testing.

Genomic determinants of motor and cognitive outcomes in Parkinson's disease.

BACKGROUND: Little is known regarding genetic factors associated with motor or cognitive outcomes in Parkinson's disease (PD). OBJECTIVE: To identify common genetic variants associated with motor and cognitive outcomes in PD. METHODS: The sample consisted of 443 PD cases included in the first genome-wide association study (GWAS) of PD. Methods included telephone interview assessments of motor and cognitive outcomes, a median 9 years following the initial clinical assessments. Analyses included Cox proportional hazard models to study the association of 198,345 single nucleotide polymorphisms (SNPs) with survival free of Hoehn and Yahr stage ≥ 4 (motor outcome), and either TICS-M ≤ 27 or AD-8 ≥ 2 (cognitive outcomes). RESULTS: The SNP rs10958605 in the C8orf4 gene had the smallest p value in analyses of the motor outcome (HR = 1.81; 95% CI = 1.42-2.31; p = 1.51 × 10(-6)). The SNP rs6482992 in the CLRN3 gene had the smallest p value in analyses of the cognitive outcome (HR = 2.03, 95% CI 1.47-2.79, p = 4.08 × 10(-6)). However, no SNP associations were significant after Bonferroni correction. The C8orf4 gene had small p values for both motor and cognitive outcomes, highlighting inflammation as a possible pathogenesis mechanism for progression in PD. CONCLUSIONS: This study suggests that common variants in several genes may be associated with motor and cognitive outcomes in PD, with biological plausibility.

Feasibility of a telephone-based intervention for support persons to help smokers quit: a pilot study.

BACKGROUND: Nonsmokers have a potentially supportive role in tobacco cessation efforts. The present study examined the feasibility, acceptability, and potential efficacy of a telephone-based intervention for nonsmoking support persons. METHODS: A total of 59 support persons (mean age = 36 years, 92% female, 95% White) were randomly assigned to a control condition (N = 30; written materials only) or to a social cognitive theory-based intervention (N = 29; written materials and 5 weekly, 20- to 30-min telephone counseling sessions). Both support persons and smokers completed assessments separately by mail at baseline and at weeks 6 (end of treatment) and 26. RESULTS: Two thirds of the smokers reported low-moderate levels of motivation to quit at baseline as assessed by the contemplation ladder. Study retention rates were excellent, with 95% of both support persons and smokers completing the week 26 assessment. Moreover, 86% of support persons in the intervention group completed all five telephone sessions. Treatment acceptability was high for both support persons and smokers. Compared with the control condition, the intervention was associated with a significant increase in support person self-efficacy to help their smoker (p = .034) and outcome expectancies (p = .025) from baseline to week 6. However, the intervention was not associated with higher smoking abstinence rates or quit attempts. DISCUSSION: The program was successful in reaching smokers with lower levels of readiness to quit. The intervention was feasible and acceptable to both support persons and smokers. Although support persons and smokers can be engaged in this type of outreach program, refinements in the intervention approach are needed to improve the smoking outcomes.

Support person intervention to promote smoker utilization of the QUITPLAN Helpline.

BACKGROUND: Effective cessation services are greatly underutilized by smokers. Only about 1.5% of smokers in Minnesota utilize the state-funded QUITPLAN Helpline. Substantial evidence exists on the role of social support in smoking cessation. In preparation for a large randomized trial, this study developed and piloted an intervention for an adult nonsmoking support person to motivate and encourage a smoker to call the QUITPLAN Helpline. METHODS: The support person intervention was developed based on Cohen's theory of social support. It consisted of written materials and three consecutive, weekly, 20-30 minute telephone sessions. Smoker calls to the QUITPLAN Helpline were documented by intake staff. RESULTS: Participants were 30 support people (93% women, 97% Caucasian, mean age 49). High rates of treatment compliance were observed, with 28 (93%) completing all three telephone sessions. The intervention was ranked as somewhat or very helpful by 77% of the support people, and 97% would definitely or probably recommend the program. Five smokers linked to a support person called the QUITPLAN Helpline. CONCLUSIONS: An intervention using natural support networks to promote smoker utilization of the QUITPLAN Helpline is both acceptable to a support person and feasible. A controlled randomized trial is under way to examine the efficacy of the intervention.

The effects of survey mode and asking about future intentions on self-reports of colorectal cancer screening.

Colorectal cancer (CRC) screening rates are often ascertained via self-reports but can be subject to overreporting bias. Asking about intention to get screened before asking about past screening may minimize overreporting of cancer screening. In a statewide survey conducted from July through October of 2005, we embedded an experiment that tested the effect of question ordering (asking about future intention to get screened before or after asking about past screening; "future first" and "future second," respectively), crossed with survey mode (mail versus telephone), on CRC screening rates. Weighted analysis focused on 752 respondents who were ages 50 years or older. We found (a) that asking about future intentions to get screened before asking about past screening (future first) statistically significantly lowers reports of past CRC screening [70.9% future second versus 58.0% future first; odds ratio (OR), 1.83; 95% confidence interval (95% CI), 1.08-3.13]; (b) that there was no main effect of survey mode; and (c) that the effect of the ordering of the future intentions item varies by survey mode. In the mailed survey, the odds of reporting past CRC screening were almost thrice greater in the future second condition compared with the future first condition (72.4% versus 49.0%, respectively; OR, 2.74; 95% CI, 1.22-6.17). In the telephone condition, the odds of reporting were only 28% higher in the future second (69.5%) condition than in the future first condition (63.9%; OR, 1.28; 95% CI, 0.64-2.57). The results suggest that asking about future intentions to get screened before the actual behavior elicits lower, and arguably more truthful reports of CRC screening but mainly in mailed surveys.

Evaluation of a Tobacco Educational Intervention for Pregnant Alaska Native Women.

Tobacco cessation interventions developed and evaluated for Alaska Native women do not exist. As part of routine clinical care provided at a prenatal visit, a brief tobacco educational intervention for Alaska Native pregnant women (N=100; mean ± SD age = 25.9±6.2 years; mean 6.3±2.6 months gestation) was piloted at the Y-K Delta Regional Hospital in Bethel, Alaska. This retrospective study reports on the evaluation of this clinical program. The intervention was consistent with the clinical practice guidelines (i.e., 5 A's - ask, advise, assess, assist, arrange), with an average duration of 20.2 ± 6.8 minutes. The self-reported tobacco abstinence rate following the intervention was 11% at the last prenatal visit and 12% at delivery. Delivering a tobacco cessation intervention at a prenatal visit is feasible, but there is a need to identify more effective interventions for Alaska Native pregnant women.

Assessing attitudes toward laxative preparation in colorectal cancer screening and effects on future testing: potential receptivity to computed tomographic colonography.

OBJECTIVE: To investigate whether removal of the laxative preparation would improve colorectal cancer (CRC) screening rates. RESPONDENTS AND METHODS: Data are from a mixed-mode mail and telephone survey of 1636 noninstitutionalized Minnesota residents who were 18 years or older that was conducted from July 15 through October 25, 2005. The overall response rate was 49%. Analysis focused on the 759 respondents who were 50 years or older. RESULTS: One third (32%) of the respondents identified the laxative preparation as the most troublesome part of CRC screening. Overall, the self-reported likelihood and anticipated timing of examination increase when the laxative preparation is removed. Both univariate and multivariate analysis showed that the odds of being "much more likely" to undergo screening in the future with a test that does not include a laxative preparation are greatest among those who have been tested previously, regard the laxative preparation as a big problem, or both. CONCLUSION: In this prospective survey, laxative preparation appeared to be a major disincentive to CRC screening. Emerging data suggest that performance of laxative-free computed tomographic colonography may represent an attractive option that removes this relatively common disincentive to CRC screening participation.