E-cigarette use reasons and associated e-cigarette use dependence among college students: A longitudinal examination.

OBJECTIVE: Previous studies have established an understanding of reasons for e-cigarette use and associated e-cigarette use patterns such as use frequency, yet the critical extension to associated e-cigarette dependence outcome remains under-researched. This study used longitudinal data to examine whether the reasons for e-cigarette use predict a higher/lower level of e-cigarette dependence. METHODS: This study recruited college students who were current e-cigarette users from Fall 2019 to Fall 2020 (four semesters) at three public universities in the Midwest and South of the U.S. Those who participated for at least two semesters were included (N = 366). Data were collected using a structured questionnaire. E-cigarette use dependence was assessed using the Penn State Electronic Cigarette Dependence Index. A linear mixed model with a random intercept and a random slope was conducted to examine the longitudinal association between reasons for e-cigarette use and dependence, controlling for demographics and other covariates. RESULTS: Participants who used e-cigarettes for relaxation (ß = 0.63, p < 0.05) and due to their good taste (ß = 0.63, p < 0.05) had a higher level of e-cigarette dependence. Participants using e-cigarettes for experimental purposes had a lower level of e-cigarette dependence (ß = -1.21, p < 0.01). CONCLUSIONS: These findings highlight the importance of addressing e-cigarette use reasons and their relationship to e-cigarette dependence. Prevention and intervention efforts aimed at developing more effective strategies should consider the various e-cigarette use reasons associated with dependence risks, such as enhancing awareness of the use dependence risk related to good taste of e-cigarettes and use for relaxation, as well as incorporating early screenings for use.

Pilot Study to Assess the Effectiveness of the Sustainable Culturally Adaptive Nutrition Program (SCAN) to Improve Adherence to the National Diabetes Prevention Program.

PURPOSE: The Sustainable Culturally Adapted Nutrition Program (SCAN) is a novel adaptation to the National Diabetes Prevention Program (NDPP) that aims to improve attendance and effectiveness. This paper presents its feasibility and impact through the initial 6-month outcomes. DESIGN: A pragmatic quasi-experimental pilot study with intervention (DPP plus SCAN) and control (DPP only) groups. SAMPLES AND INCLUSION CRITERIA: Sustainable Culturally Adapted Nutrition Program participants were recruited from federally qualified health center (FQHC) clinic patients enrolled in a NDPP in Houston, Texas. Participants needed to be (1) ≥18 years old, (2) body mass index >25, (3) no prior diagnosis of diabetes, and (4) not pregnant. INTERVENTION: Sustainable Culturally Adapted Nutrition Program cooking classes were designed to teach skills to prepare fresh produce, and utilized Motivational Interviewing (MI) techniques to encourage participants to adapt these skills for foods that were culturally important to them. OUTCOME MEASURES: (1) National Diabetes Prevention Program attendance, (2) BMI and (3) percent weight loss. ANALYSIS: We used linear mixed models to test the association between weights and NDPP attendance. RESULTS: 22 intervention and 15 control participants completed the program to the 6-month point. Intervention participants had increased DPP attendance over controls (7.14 vs 6.87 session). Intervention participants also demonstrated on average, 1.5% weight loss for each additional SCAN class attended (P = .144). CONCLUSIONS: The SCAN adaptation shows promising results for effectively increasing both NDPP attendance and weight loss.

Dependence motives and use contexts that predicted smoking cessation and vaping cessation: A two-year longitudinal study with 13 waves.

INTRODUCTION: Prior studies examining the impact of e-cigarette use, dependence, cessation motivation/goals, and environmental restriction on smoking cessation were based on cross-sectional or shorter-term longitudinal data with binary outcomes. There is also a critical knowledge gap in corresponding impact on vaping cessation. This study aims to fill in these gaps by investigating these factors' effects on speed of progression to smoking and vaping cessation. METHODS: This study conducted secondary analysis of data from 13 waves of assessment of adult cigarette users in Wisconsin from October 2015 through July 2019. Cox regression was employed to examine baseline predictors' effects on speed of progression to smoking cessation (past-month abstinence) among 405 exclusive combustible cigarette users and dual users of combustible and electronic cigarettes, as well as progression to vaping cession among 178 dual users. RESULTS: Dual use of e-cigarettes with cigarettes, lower primary dependence motives of smoking, higher secondary dependence motives of smoking, higher motivation to quit smoking, more ambitious future goals to quit smoking, and more restrictive environment for smoking all contributed to quicker progression to smoking cessation. Dual users with higher secondary dependence motives of smoking or with lower primary dependence motives of vaping progressed faster to vaping cessation. CONCLUSIONS: The findings support that nicotine dependence is product-specific with two distinct constructs: the primary dependence motives are associated with more difficulty to quit, whereas the secondary dependence motives have the opposite effect. Dual users with strong instrumental reasons for smoking may not find e-cigarettes as an effective substitute for cigarettes.

Retrospective and Real-time Measures of the Quantity of E-cigarette Use: An Ecological Momentary Assessment Study.

INTRODUCTION: Quantifying e-cigarette use is challenging because of the wide variety of products and the lack of a clear, objective demarcation of a use event. This study aimed to characterize the difference between retrospective and real-time measures of the quantity of e-cigarette use and identify the covariates that may account for discrepancies between the two types of measures. METHODS: This study analyzed data from 401 college student e-cigarette users in Indiana and Texas who responded to a web survey (retrospective) and 7-day ecological momentary assessments (EMA) (real-time) on their e-cigarette use behavior, dependence symptomatology, e-cigarette product characteristics, and use contexts from Fall 2019 to Fall 2021. Generalized linear mixed models were used to model the real-time measures of quantity offset by the retrospective average quantity. RESULTS: Although the number of times using e-cigarettes per day seems to be applicable to both retrospective and real-time measures, the number reported via EMA was 8.5 times the retrospective report. E-cigarette users with higher e-cigarette primary dependence motives tended to report more daily nicotine consumption via EMA than their retrospective reports (ie, perceived average consumption). Other covariates that were associated with discrepancies between real-time and retrospective reports included gender, nicotine concentration, using a menthol- or fruit-flavored product, co-use with alcohol, and being with others when vaping. CONCLUSIONS: The study found extreme under-reporting of e-cigarette consumption on retrospective surveys. Important covariates identified to be associated with higher than average consumption may be considered as potential targets for future vaping interventions. IMPLICATIONS: This is the first study that characterizes the direction and magnitude of the difference between retrospective and real-time measures of the quantity of e-cigarette use among young adults-the population most likely to use e-cigarettes. An average retrospective account of vaping events per day may significantly underestimate e-cigarette use frequency among young adults. The lack of insight into the degree of consumption among users with heavy primary dependence motives illustrates the importance of incorporating self-monitoring into cessation interventions.

An ecological momentary assessment study to examine covariates and effects of concurrent and simultaneous use of electronic cigarettes and marijuana among college students.

INTRODUCTION: The prevalence of concurrent and simultaneous use of e-cigarette and marijuana among college students is high. Yet, the literature was mainly based on cross-sectional surveys with emphasis on the smoking route. This is the first ecological momentary assessment (EMA) study that examined the vaping route of nicotine-marijuana co-use and the associated short-term psychological effects. METHODS: This study recruited 686 college student e-cigarette users to participate in an on-line survey and 7-day EMA. Frequent marijuana users (247) - using marijuana weekly or daily - were compared with infrequent/non-users (439) on academic performance, e-cigarette use patterns, and dependence and respiratory symptoms. EMA data from the frequent users were used to study the association between marijuana vaping and e-cigarette consumption and the short-term psychological effects of e-cigarette and marijuana use. RESULTS: The results show that e-cigarette users who frequently used marijuana tended to have lower academic performance, be involved in higher-risk use patterns, and have higher levels of e-cigarette dependence, marijuana problems, and respiratory symptoms, compared to infrequent/non-users. Marijuana vaping was associated with a higher level of e-cigarette consumption. E-cigarette use and marijuana use were both associated with higher levels of positive affect, physiological sensation, and craving for e-cigarettes. While marijuana use was linked to a lower level of negative affect, e-cigarette use did not have a significant effect. Further, none of the interaction effects between e-cigarette and marijuana use on psychological states were significant. CONCLUSIONS: The results showed additive effects of e-cigarette and marijuana use although the hypothesized synergistic effects were not supported.

Subtypes of Dual Users of Combustible and Electronic Cigarettes: Longitudinal Changes in Product Use and Dependence Symptomatology.

INTRODUCTION: Cross-sectional surveys found behavioral heterogeneity among dual users of combustible and electronic cigarettes. Yet, prior classification did not reflect dynamic interactions between cigarette and e-cigarette consumption, which may reveal changes in product-specific dependence. The contexts of dual use that could inform intervention were also understudied. METHODS: This study conducted secondary analysis on 13 waves of data from 227 dual users who participated in a 2-year observational study. The k-means method for joint trajectories of cigarette and e-cigarette consumption was adopted to identify the subtypes of dual users. The time-varying effect model was used to characterize the subtype-specific trajectories of cigarette and e-cigarette dependence. The subtypes were also compared in terms of use contexts. RESULTS: The four clusters were identified: light dual users, predominant vapers, heavy dual users, and predominant smokers. Although heavy dual users and predominant smokers both smoked heavily at baseline, by maintaining vaping at the weekly to daily level the heavy dual users were able to considerably reduce cigarette use. Yet, the heavy dual users' drop in cigarette dependence was not as dramatic as their drop in cigarette consumption. Predominant vapers appeared to engage in substitution, as they decreased their smoking and increased their e-cigarette dependence. They were also more likely to live in environments with smoking restrictions and report that their use of e-cigarettes reduced cigarette craving and smoking frequency. CONCLUSIONS: Environmental constraints can drive substitution behavior and the substitution behavior is able to be sustained if people find the substitute to be effective. IMPLICATIONS: This study characterizes subtypes of dual users based on the dynamic interactions between cigarette use and e-cigarette use as well as product-specific trajectories of dependence. The subtypes differ in not only sociodemographic characteristics but also contexts of cigarette and e-cigarette use. Higher motivation to use e-cigarettes to quit smoking and less permissive environment for smoking may promote substitution of cigarettes by e-cigarettes.

The situational contexts and subjective effects of co-use of electronic cigarettes and alcohol among college students: An ecological momentary assessment (EMA) study.

INTRODUCTION: Understanding the co-use of e-cigarettes and alcohol, including the situational contexts and subjective effects associated with co-use in real-time is necessary for validating this behavior and informing intervention. Yet, the sparse literature has built upon retrospective data. METHODS: This study recruited 686 college students who were currently using e-cigarettes from three campuses in the Midwest and South of U.S in Fall 2019-Fall 2021. An on-line survey was conducted to measure e-cigarette use patterns, GPA, e-cigarette and alcohol dependence symptoms, and respiratory symptoms. A 7-day ecological momentary assessment was used to collect real-time data on e-cigarette and alcohol use, situational contexts and subjective effects. RESULTS: Frequent drinking e-cigarette users reported more high-risk use behavior including consuming 6 + drinks/occasion and simultaneous use, and reported more e-cigarettes and alcohol related dependence symptoms and respiratory symptoms, compared to infrequent/non-drinker e-cigarette users. Alcohol quantity was positively associated with e-cigarette quantity among the high frequency drinking group. This study identified important use contexts that were associated with higher e-cigarette consumption including use of menthol or fruit flavored e-cigarettes, being in a car, and the presence of others. E-cigarette use and alcohol use both increased the levels of positive affect, physiological sensation, and craving for e-cigarettes, whereas only alcohol use significantly decreased negative affect. No interaction effects between e-cigarette use and alcohol use were found. CONCLUSIONS: The findings highlight the addiction and health risks associated with frequent co-use of e-cigarettes and alcohol, and also call for regulations on nontobacco flavorings in e-cigarette products.

Alcohol and cannabis co-use and longitudinal gray matter volumetric changes in early and late adolescence.

BACKGROUND: Previous studies have characterized the impact of substance use on cerebral structure and function in adolescents. Yet, the great majority of prior studies employed a small sample, presented cross-sectional findings, and omitted potential sex differences. METHODS: Using data based on 724 adolescents (370 females) curated from the NCANDA study, we investigated how gray matter volumes (GMVs) decline longitudinally as a result of alcohol and cannabis use. The impacts of alcohol and cannabis co-use and how these vary across assigned sex at birth and age were examined. Brain imaging data comprised the GMVs of 34 regions of interest and the results were evaluated with a Bonferroni correction. RESULTS: Mixed-effects modeling showed faster volumetric declines in the caudal middle frontal cortex, fusiform, inferior frontal, superior temporal (STG), and supramarginal (SMG) gyri, at -0.046 to -0.138 cm3 /year in individuals with prior-year alcohol and cannabis co-use, but not those engaged in alcohol or cannabis use only. These findings cannot be explained by more severe alcohol use among co-users. Further, alcohol and cannabis co-use in early versus late adolescence predicted faster volumetric decline in the STG and SMG across assigned sex at birth. CONCLUSIONS: Findings highlight the longitudinal impact of alcohol and cannabis co-use on brain development, especially among youth reporting early adolescent onset of use. The volumetric decline was noted in cortical regions in support of attention, memory, executive control, and social cognition, suggesting the pervasive effect of alcohol and cannabis co-use on brain development.

Brain insulin resistance and the therapeutic value of insulin and insulin-sensitizing drugs in Alzheimer's disease neuropathology.

The incidence of Alzheimer's disease (AD) is significantly higher in people with diabetes. Insulin and insulin receptor (IR) signaling intermediates are expressed in the brain. Insulin exerts multiple function in the brain. The role of compromised IR signaling in AD pathogenesis and the therapeutic value of insulin attract broad attention. This review summarizes the collective insulin action in the brain related to key factors of AD pathogenesis, updates the key features of insulin resistance in the AD brain and assesses the therapeutic potential of insulin and insulin-sensitizing drugs. Insulin stimulates neural growth and survival, suppresses amyloidogenic processing of the amyloid precursor protein (AßPP) and inhibits the Tau phosphorylation kinase, glycogen synthase kinase 3ß. Central nervous IR signaling regulates systemic metabolism and increases glucose availability to neurons. The expression of IR and its downstream effectors is reduced in AD brain tissues. Insulin and insulin-sensitizing drugs can improve cognitive function in AD patients and AD animal models. Systemic insulin delivery is less effective than intranasal insulin treatment. The penetrance of insulin-sensitizing drugs to the blood brain barrier is problematic and new brain-prone drugs need be developed. Insulin resistance manifested by the degradation and the altered phosphorylation of IR intermediates precedes overt AD syndrome. Type 3 diabetes as a pure form of brain insulin resistance without systemic insulin resistance is proposed as a causal factor in AD. Further research is needed for the identification of critical factors leading to impaired IR signaling and the development of new molecules to stimulate brain IR signaling.

Polygenic risk prediction based on singular value decomposition with applications to alcohol use disorder.

BACKGROUND/AIM: The polygenic risk score (PRS) shows promise as a potentially effective approach to summarize genetic risk for complex diseases such as alcohol use disorder that is influenced by a combination of multiple variants, each of which has a very small effect. Yet, conventional PRS methods tend to over-adjust confounding factors in the discovery sample and thus have low power to predict the phenotype in the target sample. This study aims to address this important methodological issue. METHODS: This study proposed a new method to construct PRS by (1) approximating the polygenic model using a few principal components selected based on eigen-correlation in the discovery data; and (2) conducting principal component projection on the target data. Secondary data analysis was conducted on two large scale databases: the Study of Addiction: Genetics and Environment (SAGE; discovery data) and the National Longitudinal Study of Adolescent to Adult Health (Add Health; target data) to compare performance of the conventional and proposed methods. RESULT AND CONCLUSION: The results show that the proposed method has higher prediction power and can handle participants from different ancestry backgrounds. We also provide practical recommendations for setting the linkage disequilibrium (LD) and p value thresholds.

Chronic pain and delinquency partially explain the effect of the DRD4 gene polymorphism on adult substance use.

Background: The dopamine receptor D4 [DRD4] has been reported to be associated with substance use. Yet, the roles that health conditions and behaviors may play in such association are understudied.Objective: This longitudinal study investigated the potential mediation effects of chronic pain and delinquency in adolescence on the association between the DRD4 2-repeat allele and substance use in adulthood. Sex, witnessing violence, and experiencing violence were also examined as potential moderators for the mediation pathways.Methods: We used the restricted and candidate gene data from the National Longitudinal Study of Adolescent to Adult Health (Waves I-IV) to conduct secondary analysis (N = 8,671; 47% male). A two-step approach was adopted to examine the mediation effects regarding four substance use outcomes in adulthood: number of lifetime alcohol use disorder symptoms, lifetime regular smoker status, past-month smoking, and lifetime "pain killer" misuse. The moderation effects were investigated using stratification and permutation.Results: The DRD4 2-repeat allele was associated with all adulthood substance use outcomes through adolescent chronic pain and delinquency (AORs/IRR range 1.08-3.78; all ps<0.01). The association between delinquency and smoking was higher among females. The association between delinquency and substance use was lower among the participants who witnessed violence in adolescence.Conclusions: This study identified modifiable mediators underlying the association between the DRD4 2-repeat allele and substance use behaviors, concluding that chronic pain and delinquency partially explain the effect of the DRD4 gene polymorphism on adult substance use.

Thai Buddhism-Based Mindfulness for Pain Management in Thai Outpatients with Cancer: A Pilot Study.

OBJECTIVE: This study aimed to evaluate Thai Buddhism-based Mindfulness (TBbM) feasibility based on recruitment and retention rates and to obtain preliminary data regarding changes (effect sizes) in pain severity and other outcomes when comparing control to intervention participants following TBbM use. METHODS: A randomized controlled trial was conducted in the Outpatient Department at Sawanpracharak Hospital, Thailand, from April 2018 to February 2019. Seventeen participants completed the pretest and posttest. Both groups (control group [n = 10] and intervention group [n = 7]) received usual care and watched a 25-min educational video about cancer pain. The intervention group participated in a 3-day mindfulness training program at a Buddhist temple and continued practicing at home for 8 weeks. Data were collected at baseline and at 1 and 2 months postintervention. RESULTS: One-hundred and thirty-five participants met the eligibility criteria; 112 (82%) declined to participate and 6 of 23 (26%) were lost to follow-up/dropped out. Control and intervention participants had an average age of 44 (± 8.77) and 56 years (± 7.41), respectively. When compared to the control group, the TBbM participants reported no statistically significant improvements in pain or other outcomes. While not statistically significant, the effect size indicated that pain did improve in the TBbM group (Cohen's d = 0.41). CONCLUSIONS: Given the suboptimal recruitment and retention rates, modification of the intervention is warranted. Further, our findings suggest that the intervention had a moderate effect on pain. To evaluate efficacy, future adequately powered studies are needed to test a more feasible TBbM intervention.

Community-based program to increase use of hearing conservation practices among farm and rural youth: a cluster randomized trial of effectiveness.

BACKGROUND: Noise exposure and associated hearing loss affects an estimated 2 million farm youth who are exposed as farm residents, farm family workers, hired workers, children of migrant or seasonal workers, and farm visitors. Risk factors for farm youth include frequent exposure to high farm noise; farm work from an early age, and exposure to high recreational noise (e.g., firearms, ATVs, and personal listening devices). METHODS: This study compared the effectiveness of two interventions and control. The programs included a community-based interactive youth educational program alone (Group A), a community-based interactive youth educational program followed by an Internet-based booster (Group B), and a no-interaction control (Group C). The study used a cluster randomized control design, with equal allocation ratio to each cluster, without blinding. Inclusion criteria included enrollment in grade 4, parental consent, English speaking, and attending a community-based educational event included in the cluster sampling. A total of 1979 youth were enrolled at 36 sites distributed across the 3 study arms in the following distribution: N = 662 in 13 sites (Group A), N = 680 in 12 sites (Group B), and N = 637 in 11 sites (Group C). RESULTS: Comparison with pre-intervention data showed no difference in intent to use hearing conservation strategies in experimental groups. However, knowledge and attitudes toward hearing conservation were improved in the groups receiving the Internet-based booster. Participants reported frequent exposure to sources of hazardous noise (e.g., loud sporting events, firecrackers, personal listening devices). CONCLUSIONS: It is feasible and acceptable to incorporate hearing health education into an already existing system designed to deliver health and safety educational programming to farm and rural youth. The program was adopted by the partner agency for dissemination to up to 100,000 youth annually. Results of this study inform future intervention studies, interventions aimed at farm youth, and interventions to increase use of hearing conservation strategies, as well as offer a base for developing programs for non-English speaking children. TRIAL REGISTRATION: Clinicaltrials.gov registration CT02472821. Date of trial registration: 06/09/2015 (retrospectively registered).

Time-varying Effects of GABRG1 and Maladaptive Peer Behavior on Externalizing Behavior from Childhood to Adulthood: Testing Gene × Environment × Development Effects.

Engagement in externalizing behavior is problematic. Deviant peer affiliation increases risk for externalizing behavior. Yet, peer effects vary across individuals and may differ across genes. This study determines gene × environment × development interactions as they apply to externalizing behavior from childhood to adulthood. A sample (n = 687; 68% male, 90% White) of youth from the Michigan Longitudinal Study was assessed from ages 10 to 25. Interactions between γ-amino butyric acid type A receptor γ1 subunit (GABRG1; rs7683876, rs13120165) and maladaptive peer behavior on externalizing behavior were examined using time-varying effect modeling. The findings indicate a sequential risk gradient in the influence of maladaptive peer behavior on externalizing behavior depending on the number of G alleles during childhood through adulthood. Individuals with the GG genotype are most vulnerable to maladaptive peer influences, which results in greater externalizing behavior during late childhood through early adulthood.

Psychometric Testing of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy 20-Item Scale Using Pooled Chemotherapy-Induced Peripheral Neuropathy Outcome Measures Standardization and Alliance for Clinical Trials in Oncology A151408 Study Data.

BACKGROUND: No criterion-standard patient-reported outcome measure of chemotherapy-induced peripheral neuropathy (CIPN) exists. OBJECTIVES: The aims of this study were to reevaluate the sensitivity, reliability, and validity of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-CIPN (QLQ-CIPN20) measure and suggest possible revisions that could strengthen it. METHODS: Cross-sectional QLQ-CIPN20 data from 8 European countries (n = 271) were pooled with data from 4 North American multisite CIPN intervention trials (n = 884). The combined sample (N = 1155) included patients with varied cancer diagnoses who had received neurotoxic chemotherapy. Item score ranges, Cronbach's α, and exploratory factor analysis were used to evaluate sensitivity, internal consistency, and structural validity. RESULTS: Individual item mean scores ranged from 1.21 to 2.34 (SD range, 0.55-1.17). All item scores encompassed the entire 1 to 4 range. We recommend that 4 items be removed because of low item-item score correlations (r < 0.30). On the basis of the remaining 16 items, 88% of the variance was explained by 2 factors whose Cronbach's α coefficients were .90 and .85. However, items lacked conceptual alignment with previously published factor structures. CONCLUSION: Using a large, diverse sample of European and North American participants, the reduced 16-item QLQ-CIPN20 is sensitive and internally consistent. However, factor analysis results revealed an unstable factor structure. IMPLICATIONS FOR PRACTICE: The use of a reliable, valid, and sensitive criterion-standard QLQ-CIPN20 variant in clinical practice settings could improve function, quality of life, and CIPN symptom control by facilitating patient reporting and thereby clinician awareness of this underrecognized consequence of cancer therapy.

Integrative approach identifies corticosteroid response variant in diverse populations with asthma.

BACKGROUND: Although inhaled corticosteroid (ICS) medication is considered the cornerstone treatment for patients with persistent asthma, few ICS pharmacogenomic studies have involved nonwhite populations. OBJECTIVE: We sought to identify genetic predictors of ICS response in multiple population groups with asthma. METHODS: The discovery group comprised African American participants from the Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-Ethnicity (SAPPHIRE) who underwent 6 weeks of monitored ICS therapy (n = 244). A genome-wide scan was performed to identify single nucleotide polymorphism (SNP) variants jointly associated (ie, the combined effect of the SNP and SNP × ICS treatment interaction) with changes in asthma control. Top associations were validated by assessing the joint association with asthma exacerbations in 3 additional groups: African Americans (n = 803 and n = 563) and Latinos (n = 1461). RNA sequencing data from 408 asthmatic patients and 405 control subjects were used to examine whether genotype was associated with gene expression. RESULTS: One variant, rs3827907, was significantly associated with ICS-mediated changes in asthma control in the discovery set (P = 7.79 × 10-8) and was jointly associated with asthma exacerbations in 3 validation cohorts (P = .023, P = .029, and P = .041). RNA sequencing analysis found the rs3827907 C-allele to be associated with lower RNASE2 expression (P = 6.10 × 10-4). RNASE2 encodes eosinophil-derived neurotoxin, and the rs3827907 C-allele appeared to particularly influence ICS treatment response in the presence of eosinophilic inflammation (ie, high pretreatment eosinophil-derived neurotoxin levels or blood eosinophil counts). CONCLUSION: We identified a variant, rs3827907, that appears to influence response to ICS treatment in multiple population groups and likely mediates its effect through eosinophils.

A hybrid method of the sequential Monte Carlo and the Edgeworth expansion for computation of very small p-values in permutation tests.

Permutation tests are very useful when parametric assumptions are violated or distributions of test statistics are mathematically intractable. The major advantage of permutation tests is that the procedure is so general that it is applicable to most test statistics. The computational expense is, however, impractical in high-dimensional settings such as genomewide association studies. This study provides a comprehensive review of existing methods that can compute very small p-values efficiently. A common issue with existing methods is that they can only be applied to a specific test statistic. To fill in the knowledge gap, we propose a hybrid method of the sequential Monte Carlo and the Edgeworth expansion approximation for a studentized statistic, which is applicable to a variety of test statistics. The simulation results show that the proposed method performs better than competing methods. Furthermore, applications of the proposed method are demonstrated by statistical analysis on the genomewide association studies data from the Study of Addiction: Genetics and Environment (SAGE).

Rasch model-based testing of the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy (QLQ-CIPN20) using Alliance for Clinical Trials in Oncology (Alliance) A151408 study data.

PURPOSE: To test the psychometric properties of the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy (QLQ-CIPN20) using Rasch-based methods. METHODS: A secondary data analysis was performed using pooled QLQ-CIPN20 data from patients (N = 1008) who had participated in any of four multi-site chemotherapy-induced peripheral neuropathy (CIPN) treatment and prevention trials. QLQ-CIPN20 responses were evaluated using a polytomous Rasch partial credit model. Data were assessed for person-item fit using the chi-square statistic, item scaling based on response proportions, threshold ordering using item characteristic curves and logit threshold locations, differential item response (DIF) (i.e., response bias) using likelihood ratio tests, and unidimensionality using cluster analysis. RESULTS: A statistically significant chi-square test indicated poor fit of the observed to the expected responses. More than 70% of the respondents reported a complete absence of six symptoms, reflecting significant floor effects and poor item scaling. Disordered/non-ordinal or narrow response thresholds were found for 11 of the 20 items. Item responses were significantly different by gender (p < 0.0001) and chemotherapy type (p < 0.0001). Cluster analysis findings suggest that the QLQ-CIPN20 is a unidimensional scale due to the absence of item clusters. CONCLUSIONS: Rasch model testing revealed psychometric weaknesses that could be addressed by revising the QLQ-CIPN20's problematic items and response options. Alternatively, perhaps the new gold standard CIPN measurement approach in future intervention trials should involve use of only the best items, which would also allow comparisons across previous trials that utilized the QLQ-CIPN20.

Chemotherapy-Induced Peripheral Neuropathy: Use of an Electronic Care Planning System to Improve Adherence to Recommended Assessment and Management Practices.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is often inadequately assessed and managed by advanced practice providers. OBJECTIVES: The aim is to explore the impact of CIPN assessment training and electronic care planning system (CPS) use on CIPN assessment documentation and guidelines adherence. METHODS: The authors used a pre-/post-test, prospective design with two retrospective chart reviews. Six providers received CIPN assessment training and used the CPS to manage CIPN for 75 women receiving neurotoxic chemotherapy. FINDINGS: CPS use significantly improved documentation of numbness and nonpainful CIPN management strategies but had no effect on documentation of additional assessment variables or painful CIPN management.

Sleep and self-care correlates before and after implantation of a left-ventricular assist device (LVAD).

The impact of sleep on LVAD patients' self-care behaviors is unknown. This study examined the patterns and changes of patients sleep quality (SQ), daytime sleepiness (DS), instrumental activities of daily living (IADL), and self-care capability (SCC) before and after LVAD. In addition, the relationships among these variables were explored. This observational study consisted of 38 subjects from two VAD Centers in Michigan. The subjects completed self-reported demographics and psychometrically sound SQ, DS, IADL, and SCC questionnaires before LVAD implant and at 1, 3, and 6 months after implant. Data were analyzed using descriptive statistics, linear mixed models, and partial least square models. Subjects (mean age, 56.3 ± 10.3 years) were predominantly white (63%), male (68%), married (60%), and living with caregivers (92%). Over 70% had axial flow LVADs implanted as bridge-to-transplant (55%). Subjects' SQ was poor throughout the study period, along with high normal-to-excessive levels of DS. Problems with IADL before implant were significantly reduced at 1 through 6 months after implant. SCC ranged from "good" to "excellent" before and after implant. Significant relationships between SQ and IADL (ß = 0.43, p < 0.01) and DS and SCC (ß = - 0.62, p < 0.01) were found. In conclusion, poor SQ and high degrees of DS were prevalent before and up to 6 months after LVAD implant. The data inferred that the improvement in IADL was associated with an improvement in SQ. Research is needed to clarify the negative impact of DS on SCC and explain the contributions of caregivers on patients' SCC over time.