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.

Does α-synuclein have a dual and opposing effect in preclinical vs. clinical Parkinson's disease?

α-Synuclein gene (SNCA) multiplications cause familial parkinsonism and allele-length polymorphisms within the SNCA dinucleotide repeat REP1 increase the risk for developing Parkinson's disease (PD). Since SNCA multiplications increase SNCA expression, and REP1 genotypes that increase the risk of developing PD show increased SNCA expression in cell-culture systems, animal models, and human blood and brain, PD therapies seek to reduce SNCA expression. We conducted an observational study of 1098 PD cases to test the hypothesis that REP1 genotypes correlated with reduced SNCA expression are associated with better motor and cognitive outcomes. We evaluated the association of REP1 genotypes with survival free of Hoehn and Yahr stages 4 or 5 (motor outcome) and of Modified Telephone Interview for Cognitive Status score ≤27 or Alzheimer's Disease Dementia Screening Interview score ≥2 (cognitive outcome). Median disease duration at baseline was 3.3 years and median lag time from baseline to follow-up was 7.8 years. Paradoxically, REP1 genotypes associated with increased risk of developing PD and increased SNCA expression were associated with better motor (HR = 0.87, p = 0.046, covariate-adjusted age-scale analysis; HR = 0.85, p = 0.020, covariate-adjusted time-scale analysis) and cognitive outcomes (HR = 0.90, p = 0.12, covariate-adjusted age-scale analysis; HR = 0.85, p = 0.023, covariate-adjusted time-scale analysis). Our findings raise the possibility that SNCA has a dual, opposing, and time-dependent role. This may have implications for the development of therapies that target SNCA expression.

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.

Comprehensive research synopsis and systematic meta-analyses in Parkinson's disease genetics: The PDGene database.

More than 800 published genetic association studies have implicated dozens of potential risk loci in Parkinson's disease (PD). To facilitate the interpretation of these findings, we have created a dedicated online resource, PDGene, that comprehensively collects and meta-analyzes all published studies in the field. A systematic literature screen of -27,000 articles yielded 828 eligible articles from which relevant data were extracted. In addition, individual-level data from three publicly available genome-wide association studies (GWAS) were obtained and subjected to genotype imputation and analysis. Overall, we performed meta-analyses on more than seven million polymorphisms originating either from GWAS datasets and/or from smaller scale PD association studies. Meta-analyses on 147 SNPs were supplemented by unpublished GWAS data from up to 16,452 PD cases and 48,810 controls. Eleven loci showed genome-wide significant (P < 5 × 10(-8)) association with disease risk: BST1, CCDC62/HIP1R, DGKQ/GAK, GBA, LRRK2, MAPT, MCCC1/LAMP3, PARK16, SNCA, STK39, and SYT11/RAB25. In addition, we identified novel evidence for genome-wide significant association with a polymorphism in ITGA8 (rs7077361, OR 0.88, P  =  1.3 × 10(-8)). All meta-analysis results are freely available on a dedicated online database (www.pdgene.org), which is cross-linked with a customized track on the UCSC Genome Browser. Our study provides an exhaustive and up-to-date summary of the status of PD genetics research that can be readily scaled to include the results of future large-scale genetics projects, including next-generation sequencing studies.

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.

Survey-related experiential and attitudinal correlates of future health survey participation: results of a statewide survey.

OBJECTIVE: To determine the survey-related experiential and attitudinal correlates of future health-related survey participation. PARTICIPANTS AND METHODS: From July 21, 2005, through October 25, 2005, we conducted a mixed-mode mail and telephone survey of 1636 noninstitutionalized Minnesota residents aged 18 years or older. The overall response rate was 49%. We examined the unadjusted effect of each independent variable on the likelihood of future participation in health-related surveys using univariate logistic regression and discerned the relative contribution of the different variables with multivariate logistic regression analysis. RESULTS: Respondents were asked to complete an average of 4.5 different surveys in the year before the current survey; approximately a quarter of the respondents perceived these surveys to be burdensome. The likelihood of future participation in health-related surveys was negatively related to good health status, a busy schedule, and perceptions that the surveys were too long. Respondents were more than twice as likely to indicate that they would participate in a future health-related survey if they knew the organization doing the survey. CONCLUSION: For health-related surveys, investigators should remain mindful of people's busy schedules and keep their surveys as short as possible. Further research is needed to clarify whether the decision to participate in a survey hinges more on knowing the organization paying to have a survey performed (the sponsor) or the survey vendor collecting the data.

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.

Selected questionnaire size and color combinations were significantly related to mailed survey response rates.

OBJECTIVE: To determine the degree to which mailed survey response rates, response times, and nonresponse bias are affected by questionnaire size and color. STUDY DESIGN AND SETTING: Questionnaires were mailed to a random sample of 2,000 Mayo Clinic patients in one of four size/color "test" groups. One thousand three hundred nine surveys were completed, approximately two-thirds in each group. RESULTS: A small (6 (1/8) x 8 (1/4) in) questionnaire booklet on white paper had a higher response rate (68.4%) than a similarly sized questionnaire on blue paper (62.3%). A large (8 (1/4) x 11 in) questionnaire on white paper had a 62.7% rate, whereas a large, blue questionnaire had a response rate of 68.6%. Median response times did not differ by questionnaire size/color. No evidence of differential nonresponse bias was observed across the four test groups. CONCLUSION: This study supports the use of a small/white questionnaire format advocated by the Total Design Method advanced by Don Dillman at Washington State University. We observed a favorable response rate for a large questionnaire printed on blue paper; however, if time and resources are limited, use of a small/white questionnaire appears preferable.

The HIPAA authorization form and effects on survey response rates, nonresponse bias, and data quality: a randomized community study.

BACKGROUND: There has been speculation that the Health Insurance Portability and Accountability Act (HIPAA) has muted participation in research but little direct evidence to substantiate those claims exists. OBJECTIVE: To evaluate the effects of including a HIPAA authorization form (HAF) on multiple measures of survey performance. RESEARCH DESIGN, SUBJECTS: A community survey of Olmsted County, Minnesota residents conducted between September 2005 and April 2006. A total of 6939 cases were randomly assigned to 2 experimental conditions where half of the subjects received a 1-page HAF (n = 3469) and the other half did not (n = 3470). MAIN OUTCOME MEASURES: Response rate, nonresponse bias, and data quality. RESULTS: At the end of data collection, a response rate of 39.8% was observed in the HAF condition and 55.0% in the No HAF condition (P < 0.0001). There was a negligible but statistically significant (P < or = 0.001) over-representation of males in the No HAF condition but no difference in the amount of missing data between the 2 groups. However, reports of general health and the percentage of respondents indicating that they were nonsmokers were both significantly (P < or = 0.01) lower in the No HAF condition than in the HAF condition. CONCLUSIONS: Inclusion of a minimally burdensome version of the HAF reduced survey response rates by up to 15 percentage points. This could have implications for a study's statistical power. There was little evidence that the form affected nonresponse bias or data quality.

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.

Internet use by patients in an inflammatory bowel disease specialty clinic.

BACKGROUND: Patient education is known to improve satisfaction in and participation with treatment. A careful assessment of internet use by inflammatory bowel disease (IBD) patients to gather information has not been reported. Our aim was to evaluate internet use to gather general health- and disease-specific information in patients presenting to an IBD clinic. METHODS: A cross-sectional anonymous survey using a convenience sample of patients (N = 175) at a tertiary-care institution's IBD clinic was performed. RESULTS: In all, 169 surveys (97%) were returned for analysis. The median age was 46 (17-84), 83 men and 81 women (5 missing). In known IBD patients (87%), 85 (50%) had Crohn's disease and 62 (37%) ulcerative colitis; 81% of patients had home internet access. The most common information sources were: gastroenterologists (59%), internet (54%), and primary-care physicians (54%). Ninety-two patients (54%) used the internet to gather IBD-specific information. Age-specific use (<40, 40-65, >65) was 73%, 48%, 37.5%, respectively. There was a significant positive association between level of education and internet use (P < 0.0001), but not with income. Internet sites most commonly visited were organization- or institution-specific. Factors that most influenced a user's choice of an internet site were noncommercial status (59%) and ease of use (53%). The majority of patients (57%) rated internet information "trustworthy" to "very trustworthy." CONCLUSIONS: Over half of patients in an IBD clinic used the internet to gather IBD-specific information. Use was inversely associated with age and positively correlated with education level. There was no income association. These findings suggest web-based IBD information may become increasingly important in the future.

Mixing web and mail methods in a survey of physicians.

OBJECTIVE: To assess the effects of two different mixed-mode (mail and web survey) combinations on response rates, response times, and nonresponse bias in a sample of primary care and specialty internal medicine physicians. DATA SOURCES/STUDY SETTING: Primary data were collected from 500 physicians with an appointment in the Mayo Clinic Department of Medicine (DOM) between February and March 2005. STUDY DESIGN: Physicians were randomly assigned to receive either an initial mailed survey evaluating the Electronic Medical Record (EMR) with a web survey follow-up to nonrespondents or its converse-an initial web survey followed by a mailed survey to nonrespondents. Response rates for each condition were calculated using standard formula. Response times were determined as well. Nonresponse bias was measured by comparing selected characteristics of survey respondents to similar characteristics in the full sample frame. In addition, the distributions of results on key outcome variables were compared overall and by data collection condition and phase. PRINCIPAL FINDINGS: Overall response rates were somewhat higher in the mail/web condition (70.5 percent) than in the web/mail condition (62.9 percent); differences were more pronounced before the mode switch prior to the mailing to nonrespondents. Median response time was 2 days faster in the web/mail condition than in the mail/web (median=5 and 7 days, respectively) but there was evidence of under-representation of specialist physicians and those who used the EMR a half a day or less each day in the web/mail condition before introduction of the mailed component. This did not translate into significant inconsistencies or differences in the distributions of key outcome variables, however. CONCLUSIONS: A methodology that uses an initial mailing of a self-administered form followed by a web survey to nonrespondents provides slightly higher response rates and a more representative sample than one that starts with web and ends with a mailed survey. However, if the length of the data collection period is limited and rapid response is important, perhaps the web survey followed by a mailed questionnaire is to be preferred. Key outcome variables appear to be unaffected by the data collection method.