Mericitabine and ritonavir-boosted danoprevir with or without ribavirin in treatment-naive HCV genotype 1 patients: INFORM-SVR study.

BACKGROUND & AIMS: Safety and tolerability of peginterferon-based hepatitis C virus (HCV) infection therapy remains suboptimal, even when direct-acting antiviral agents are added. This study assessed the efficacy, safety and tolerability of mericitabine combined with ritonavir-boosted danoprevir (danoprevir/r) ± ribavirin for up to 24 weeks in treatment-naïve HCV genotype (G)1 infected patients. METHODS: Patients received twice daily mericitabine (1000 mg) and danoprevir/r (100 mg/100 mg) plus either ribavirin (1000/1200 mg/day; Arm A) or placebo (Arm B) for 12 or 24 weeks. Patients with HCV RNA <43 IU/ml between Weeks 2 and 8 and HCV RNA <15 IU/ml at Week 10 were rerandomized (1:1) at Week 12 to discontinue/continue assigned regimens until Week 24. Because of unacceptable relapse rates in both 12-week arms and in ribavirin-free Arm B, treatment was extended to 24 weeks and patients in Arm B received peginterferon alfa-2a/ribavirin. The primary outcome was sustained virological response 24 weeks after end of treatment (SVR24). RESULTS: In Arm A, the SVR24 rate in patients receiving 24 weeks of therapy was 37.9% (25/66); 63.6% (14/22) in G1b and 25.0% (11/44) in G1a patients. Virologic breakthrough and relapse were associated with danoprevir-resistant virus in most cases. The mericitabine-resistance mutation (NS5BS282T) was detected in two patients bearing dual resistant virus NS3 R155K/NS5B S282T and dual resistance mutation L159F/L320F in one patient. Treatment was safe and well tolerated. CONCLUSIONS: Mericitabine, danoprevir/r plus ribavirin for 24 weeks were safe and well tolerated. However, SVR rates were poor, achieving rates of only 25.0% in G1a and 63.6% in G1b patients.

Understanding the effect of the HCV polymerase inhibitor mericitabine on early viral kinetics in the phase 2 JUMP-C and PROPEL studies.

AIMS: The aim was to evaluate early viral kinetics in patients receiving mericitabine [hepatitis C virus (HCV) nucleoside polymerase inhibitor] with peginterferon alfa-2a (40KD) and ribavirin in two clinical trials (PROPEL and JUMP-C). METHODS: We examined rapid virological responses (RVRs; week 4 HCV RNA <15 IU ml(-1) ) and complete early virological responses (cEVR; week 12 HCV RNA <15 IU ml(-1) ) in HCV genotype 1/4-infected patients receiving mericitabine (500 or 1000 mg) or placebo twice daily plus peginterferon alfa-2a and ribavirin. RESULTS: Among IL28B rs12979860 CC genotype patients receiving 500 or 1000 mg mericitabine or placebo, respectively, RVR rates were 64.3% (95% confidence interval: 38.8-83.7%), 95.1% (83.9-98.7%) and 33.3% (20.2-49.7%), and cEVR rates were 100% (78.5-100%), 100% (91.4-100%) and 80.6% (65.0-90.3%). Among non-CC genotype patients, RVR rates were 26.5% (14.6-43.1%), 52.3% (43.0-61.3%) and 5.7% (2.2-13.8%), and cEVR rates were 76.5% (60.0-87.6%), 84.6% (76.6-90.1%) and 28.6% (19.3-40.1%), respectively. In multiple regression analysis, IL28B genotype (P < 0.0001), mericitabine dose (P < 0.0001) and bodyweight (P = 0.0009) were associated with first-phase (α) slope (change in log10 HCV RNA from baseline to week 1). CONCLUSIONS: Mericitabine-containing triple therapy reduces the impact of IL28B genotype on RVR and cEVR compared with peginterferon alfa-2a and ribavirin dual therapy. The IL28B genotype, mericitabine dose and bodyweight are the most important factors associated with the α slope, and there is no evidence of a pharmacokinetic drug-drug interaction between mericitabine and ribavirin.

Immunogenicity of Atezolizumab: Influence of Testing Method and Sampling Frequency on Reported Anti-drug Antibody Incidence Rates.

Measurement of anti-drug antibodies (ADA) to assess the incidence of ADA in a clinical trial is a critical step in immunogenicity assessment during the development of a protein therapeutic. We developed novel graphical approaches to illustrate clinical trial ADA data for the PD-L1 inhibitor atezolizumab (Tecentriq) that included a systematic analysis of the impact of the timing of ADA sampling and ADA assay drug tolerance on reported ADA incidence. We found that approaches used across the industry for ADA incidence analysis provide a limited view of immunogenicity in oncology studies, where ADA detection may be confounded by both drug dosage and patient attrition. Moreover, these approaches can miss important temporal information about the immune response. Our results demonstrated that the methodology of ADA assessment for the atezolizumab program was specifically designed to capture most ADA responses to ensure accurate reporting of ADA incidence. We further showed that the use of sparse sampling and/or ADA test methods with insufficient drug tolerance may result in a significant underreporting of ADA incidence. We conclude that the comparison of ADA incidence between different drugs can be highly misleading and that a test method with appropriate sensitivity in the presence of the drug and a clinical sampling scheme that is aligned with ADA responses to a drug is required to accurately report ADA incidence.

Development and Psychometric Validation of the 27 Item Zarit Caregiver Interview for Alzheimer's Disease (ZCI-AD-27).

BACKGROUND: Caring for an individual with Alzheimer's disease (AD) is an allencompassing challenge that affects daily life. Assessment of the care partner experience is needed to support the development and evaluation of successful interventions for people with AD and their care partners. We developed the 27-item Zarit Caregiver Interview for Alzheimer's Disease (ZCI-AD-27) to assess the impact of informal caregiving in the context of AD. OBJECTIVE: We assessed the psychometric validity of the ZCI-AD-27 in a population of care partners for individuals with moderate AD, and established thresholds for meaningful score change. METHODS: Secondary data were obtained from informal care partners of participants in a clinical trial (NCT01677754). Psychometric analyses were conducted to assess validity, reliability, and responsiveness of the ZCI-AD-27. Anchor-based and distribution-based methods were performed to determine clinically meaningful score change. RESULTS: The ZCI-AD-27 had a 12-domain factor structure, including a second-order domain termed Humanistic impact that included four key domains (Physical, Emotional, Social, and Daily life) as confirmed by confirmatory factor analysis with the adequate fit. Internal consistency (Cronbach's alpha ranging from 0.66 to 0.93 for domains), convergent validity, and discriminant validity indicated the good performance of the ZCI-AD-27. Known-groups validity analyses showed a greater impact on care partners with increasing disease severity. Responsiveness results demonstrated that the ZCI-AD- 27 is sensitive to change over time and meaningful change analyses indicated a range of meaningful score changes in this population. CONCLUSION: The ZCI-AD-27 is a comprehensive, psychometrically valid measure to assess the impact of caring for individuals with moderate AD.

Evaluation of atezolizumab immunogenicity: Efficacy and safety (Part 2).

Antibody therapeutics can be associated with unwanted immune responses resulting in the development of anti-drug antibodies (ADA). Optimal methods to evaluate the potential effects of ADA on clinical outcomes in oncology are not well established. In this study, we assessed efficacy and safety, based on ADA status, in patients from over 10 clinical trials that evaluated the immune checkpoint inhibitor atezolizumab as a single agent or as combination therapy for several types of advanced cancers. ADA can only be observed post randomization, and imbalances in baseline prognostic factors can confound the interpretation of ADA impact. We applied methodology to account for the confounding effects of baseline clinical characteristics and survivorship bias on efficacy. Adjusted meta-analyses revealed that despite numerical differences in overall survival and progression-free survival between ADA-positive and ADA-negative patients from some studies, ADA-positive patients from studies with an overall treatment effect derived benefit from atezolizumab, compared with their adjusted controls. Based on large, pooled populations from atezolizumab monotherapy or combination studies, unadjusted descriptive analyses did not identify a clear relationship between ADA status and frequency or severity of adverse events. Data also suggested that any ADA impact is not driven by neutralizing activity. Collectively, this exploratory analysis suggests that the potential for ADA development should not impact treatment decisions with atezolizumab.

Evaluation of atezolizumab immunogenicity: Clinical pharmacology (part 1).

Baseline patient characteristics and prognostic factors are important considerations in oncology when evaluating the impact of immunogenicity on pharmacokinetics (PK) and efficacy. Here, we assessed the impact of anti-drug antibodies (ADA) on the PK of the immune checkpoint inhibitor atezolizumab (an anti-PD-L1 monoclonal antibody). We evaluated data from ≈ 4500 patients from 12 clinical trials across different tumor types, treatment settings, and dosing regimens. In our dataset, ~ 30% of patients (range, 13-54%) developed treatment-emergent ADA, and in vitro neutralizing antibodies (NAb) were seen in ~ 50% of ADA-positive (+) patients. Pooled time course data showed a trend toward lower atezolizumab exposure in ADA+ patients, which was more pronounced in ADA+/NAb+ patients. However, the atezolizumab concentration distributions overlapped, and drug concentrations exceeded 6 µg/ml, the target concentration required for receptor saturation, in greater than 95% of patients. Patients had sufficient exposure regardless of ADA status. The dose selected to allow for dosing over effects from ADA resulted in a flat exposure-response relationship. Analysis of study results by ADA titer showed that exposure and overall survival were not affected in a clinically meaningful way. High tumor burden, low albumin, and high CRP at baseline showed the greatest association with ADA development but not with subsequent NAb development. These imbalanced factors at baseline can confound analysis of ADA impact. ADA increases atezolizumab clearance minimally (9%), and its impact on exposure based on the totality of the clinical pharmacology assessment does not appear to be clinically meaningful.

Cost-effectiveness of obinutuzumab plus bendamustine followed by obinutuzumab monotherapy for the treatment of follicular lymphoma patients who relapse after or are refractory to a rituximab-containing regimen in the US.

AIMS: Obinutuzumab (GA101, G) was approved in February 2016 by the US Food and Drug Administration to treat follicular lymphoma (FL) patients who relapsed after, or are refractory to (R/R), a rituximab-containing regimen (R/R-rituximab). In the GADOLIN trial, R/R-rituximab patients who received G plus bendamustine (B) followed by G-monotherapy (G + B) for up to 2 years had significantly improved progression-free survival and overall survival compared to patients receiving B-monotherapy. This study estimated the cost-effectiveness of G + B vs B-monotherapy for R/R-rituximab FL patients from a US payer perspective. MATERIALS AND METHODS: Patient outcomes were simulated using a 3-state area under the curve model including progression-free survival, progressive disease, and death. This study used R/R-rituximab data from the National LymphoCare Study to extrapolate the GADOLIN trial's refractory FL progression-free and overall survival data to a R/R-rituximab FL population. Drug utilization and adverse events were based on trial data, and costs were based on Medicare reimbursements and drug wholesale acquisition costs in 2016. Utility estimates were derived from published literature. Post-progression treatment costs were based on observed post-progression therapies in GADOLIN. Sensitivity analyses were conducted to assess model uncertainty. RESULTS: G + B resulted in an increase in quality-adjusted life years relative to B-monotherapy of 1.24 (95% CR = 0.61-1.87); the incremental total cost was $58,100 (95% CR = $54,500-$61,500). The incremental cost-effectiveness ratio was $47,000 per QALY gained, and, based on probabilistic simulations, there was a 98% probability that G + B was cost-effective at the $100,000 per QALY threshold. LIMITATIONS AND CONCLUSIONS: This US-based analysis suggests that treatment with G + B compared to B-monotherapy is likely cost-effective in R/R-rituximab FL patients. Modeling a R/R-rituximab population based on a synthesis of GADOLIN and the National LymphoCare Study data introduces uncertainty in the analysis. However, the findings were robust to sensitivity analyses.

Do children with asthma and their parents agree on household ETS exposure? Implications for asthma management.

The adverse consequences of passive smoking have spurred efforts to reduce environmental tobacco smoke (ETS) exposure among children, particularly in the home. For children with asthma, teaching them to avoid tobacco smoke at home is an important element of patient self-management. This strategy assumes that children can accurately assess household smoking behaviors and the level of their own exposure in the home. This study compared child and parental assessments of household smoking behaviors in an urban, low-income and largely ethnic minority sample of asthmatic children and their parents. While there was general parent-child agreement on the smoking status of household members, there was less agreement on duration of household smoking and the child's exposure to ETS. Objective validation measures (cotinine, nicotine) suggest that parents were better able than their children to assess hours of indoor smoking. Children's assessment of the extent of exposure to ETS may be problematic, with important implications for asthma patient self-management efforts.

Children's exposure to environmental tobacco smoke in the home: comparison of urine cotinine and parental reports.

The authors examined the relationship between parent-reported estimates of children's exposure to environmental tobacco smoke (ETS) in the home and children's urinary cotinine levels. Data were collected from a largely ethnic minority, low-income, urban sample of households in which a child had asthma and at least 1 household member smoked. Information about level of household smoking restriction, parental smoking status, and number of cigarettes smoked per day accounted for approximately 45% of the variance in cotinine concentration. Detailed information about the duration of household smoking or children's ETS exposure added no additional significant information. Questionnaires eliciting detailed information about smoking habits and children's ETS exposure may be no better at predicting children's urinary cotinine levels than simpler surveys that inquire about smoking restrictions in the home, parental smoking status, and number of cigarettes smoked at home per day.

Predictive impact of circulating vascular endothelial growth factor in four phase III trials evaluating bevacizumab.

PURPOSE: We evaluated the prognostic and predictive use of circulating VEGF-A levels in phase III trials of bevacizumab in colorectal cancer, lung cancer, and renal cell carcinoma. METHODS: Baseline plasma samples from 1,816 patients were analyzed for VEGF-A using an ELISA, which recognizes the major isoforms with equivalent sensitivity. HR and 95% confidence intervals (CI) for study end points were estimated using Cox regression analysis. A subset of matched archival tumor samples was analyzed for VEGF-A expression using in situ hybridization. RESULTS: Higher VEGF-A levels showed trends toward adverse prognostic significance in the control arms of multiple trials, reaching statistical significance for overall survival (OS) in AVF2107 (highest vs. lowest 50%: HR = 1.76; 95% CI, 1.28-2.41), AVAiL (HR = 1.52; 95% CI, 1.16-2.00), and AVOREN (HR = 1.67; 95% CI, 1.18-2.36). In predictive analyses, the HRs for progression-free survival were similar across low and high VEGF-A subgroups and favored bevacizumab-containing treatment. In the low VEGF-A subgroups, HRs (95% CIs) were 0.61 (0.43-0.87) in AVF2107, 0.71 (0.43-1.16) in E4599, 0.74 (0.59-0.94) in AVAiL (low-dose), 0.89 (0.70-1.13) in AVAiL (high-dose), and 0.56 (0.40-0.78) in AVOREN. Analyses of OS data have shown similar results. No correlation between primary tumor VEGF-A expression and plasma VEGF-A levels was observed. CONCLUSIONS: In this comprehensive evaluation, pretreatment total circulating VEGF-A was prognostic for outcome in metastatic colorectal, lung, and renal cell cancers, but it was not predictive for bevacizumab-based treatment benefit.

Evaluation of pharmacokinetics, user handling, and tolerability of peginterferon alfa-2a (40 kDa) delivered via a disposable autoinjector device.

BACKGROUND: Peginterferon alfa-2a (40 kDa) is currently administered using a prefilled syringe. The peginterferon alfa-2a disposable autoinjector is a new safety-engineered device designed to facilitate injection and reduce the risk of needlestick injuries. The analysis of two open-label Phase I trials evaluated the pharmacokinetics, successful administration, and tolerability of peginterferon alfa-2a when using the autoinjector. The studies were performed to support the filing and registration of the autoinjector device. METHODS: In trial 1, 50 healthy adult subjects received one 180 µg dose of peginterferon alfa-2a via the autoinjector. Serial blood samples were collected predose, up to 336 hours following drug administration, and at follow-up (28 ± 3 days post-dosing) for noncompartmental pharmacokinetic analysis. Trial 2 randomized 60 adult patients with chronic hepatitis C to 180 µg peginterferon alfa-2a once weekly by the autoinjector or prefilled syringe for 3 weeks followed by the alternative device (prefilled syringe or autoinjector, respectively) for 3 weeks. Patients also received ribavirin. Administration by the devices was evaluated under direct observation by a study staff member and by patient subjective assessment. RESULTS: In trial 1, following a single dose of peginterferon alfa-2a, the maximum plasma concentration was 16.1 ± 5.3 ng/mL (mean ± standard deviation), and area under the concentration time curve (0-168 hours) was 1996 ± 613 ng · hour/mL, similar to that reported using a vial/syringe or prefilled syringe. In trial 2, few patients showed handling difficulties with either device. Generally, patients were observed to be more satisfied and confident, followed instructions better, and successfully initiated injection with the autoinjector versus the prefilled syringe. Patients reported the autoinjector to be more convenient and easier to use. No pain or discomfort was experienced using the autoinjector. The autoinjector safety profile was consistent with that known for peginterferon alfa-2a/ribavirin. CONCLUSION: These results indicate that peginterferon alfa-2a can be successfully and safely delivered via the autoinjector and that the device is easy to handle.

Pharmacokinetic analysis of irinotecan plus bevacizumab in patients with advanced solid tumors.

PURPOSE: The purpose of this study was to evaluate the effect of bevacizumab on the pharmacokinetics (PK) of irinotecan and its active metabolite. Exploratory analyses of the impact of variability in uridine diphosphate glucuronosyltransferase 1A (UGT1A) genes on irinotecan metabolism and toxicity were conducted. METHODS: This was an open-labeled, fixed-sequence study of bevacizumab with FOLFIRI (irinotecan, leucovorin, and infusional 5-fluorouracil). Pharmacokinetic assessments were conducted in cycles 1 and 3. RESULTS: Forty-five subjects were enrolled. No difference in dose-normalized AUC(0-last) for irinotecan and SN-38 between irinotecan administered alone or in combination with bevacizumab was identified. Leukopenia was associated with higher exposure to both irinotecan and SN-38. UGT1A1 polymorphisms were associated with variability in irinotecan PK. Gastrointestinal toxicity was associated with UGT1A6 genotype. No other associations between UGT1A genotypes and toxicity were detected. CONCLUSION: Bevacizumab does not affect irinotecan PK when administered concurrently. A variety of pharmacogenetic relationships may influence the pharmacokinetics of irinotecan and its toxicity.

Robustness of a multivariate normal approximation for imputation of incomplete binary data.

Multiple imputation has become easier to perform with the advent of several software packages that provide imputations under a multivariate normal model, but imputation of missing binary data remains an important practical problem. Here, we explore three alternative methods for converting a multivariate normal imputed value into a binary imputed value: (1) simple rounding of the imputed value to the nearer of 0 or 1, (2) a Bernoulli draw based on a 'coin flip' where an imputed value between 0 and 1 is treated as the probability of drawing a 1, and (3) an adaptive rounding scheme where the cut-off value for determining whether to round to 0 or 1 is based on a normal approximation to the binomial distribution, making use of the marginal proportions of 0's and 1's on the variable. We perform simulation studies on a data set of 206,802 respondents to the California Healthy Kids Survey, where the fully observed data on 198,262 individuals defines the population, from which we repeatedly draw samples with missing data, impute, calculate statistics and confidence intervals, and compare bias and coverage against the true values. Frequently, we found satisfactory bias and coverage properties, suggesting that approaches such as these that are based on statistical approximations are preferable in applied research to either avoiding settings where missing data occur or relying on complete-case analyses. Considering both the occurrence and extent of deficits in coverage, we found that adaptive rounding provided the best performance.

Do deaf and hard of hearing youth need antitobacco education?

Little research has focused on tobacco use among deaf and hard of hearing youth. Findings are reported from a first-ever tobacco-related survey, completed by 226 California middle and high school students using either a written questionnaire or the Interactive Video Questionnaire, an interactive multimedia computer video technology. Rates for current smoking (3.1%), ever smoking (45.1%), and multiple types of tobacco use (10.6%) were found to be lower than among high school students generally; mainstreamed students were likelier to have ever tried smoking than their deaf school peers (57.8% vs. 31.8%). No statistically significant associations were found between ever smoking and race/ethnicity, gender, school performance, or prelingual vs. postlingual deafening; a quarter of the sample experienced occasional peer pressure to use tobacco products. Tobacco use covariates, exposure to cigarette marketing and antismoking programming, and tobacco education needs of deaf and hard of hearing youth are discussed.

Assessing the impact of cancer: development of a new instrument for long-term survivors.

OBJECTIVE: To develop and evaluate a new instrument that measures aspects of long-term survivorship not measured by existing tools. METHODS: In qualitative interviews, 47 long-term cancer survivors (LTS) detailed ways that cancer has impacted their lives. Content analysis resulted in the creation of 325 candidate items for inclusion in a new Impact of Cancer (IOC) instrument. Following expert review, item reduction and pilot testing, 81 items were administered with other established health status and quality of life (QOL) instruments to 193 LTS of breast, prostate, colorectal cancers and lymphoma. Internal consistency reliability and validity of newly-derived scales was assessed. RESULTS: Factor analysis of items using a priori QOL domains resulted in the derivation of ten new and specific subscales: Health Awareness, Body Changes, Health Worries, Positive and Negative Self-Evaluation, Positive and Negative Life Outlook, Social Life Interferences, Relationships, and Meaning of Cancer. Internal consistency measurements for these subscales ranged from 0.67 to 0.89. Expected associations within and among the IOC subscales and standardized measures of health status and QOL were observed, as were some unexpected findings. CONCLUSIONS: Psychometric analysis indicated that this initial version of the Impact of Cancer instrument measures distinct and relevant constructs for LTS. Future work is necessary to confirm the factor structure, responsiveness and further validation of the instrument.

Fatigue in long-term breast carcinoma survivors: a longitudinal investigation.

BACKGROUND: A longitudinal study was designed to evaluate the prevalence, persistence, and predictors of posttreatment fatigue in breast carcinoma survivors. METHODS: A sample of 763 breast carcinoma survivors completed questionnaires at 1-5 and 5-10 years after diagnosis, including the RAND 36-item Health Survey, Center for Epidemiological Studies - Depression scale (CES-D), Breast Cancer Prevention Trial Symptom Checklist, and demographic and treatment-related measures. RESULTS: Approximately 34% of study participants reported significant fatigue at 5-10 years after diagnosis, which is consistent with prevalence estimates obtained at 1-5 years after diagnosis. Approximately 21% reported fatigue at both assessment points, indicating a more persistent symptom profile. Longitudinal predictors of fatigue included depression, cardiovascular problems, and type of treatment received. Women treated with either radiation or chemotherapy alone showed a small improvement in fatigue compared with those treated with both radiation and chemotherapy. CONCLUSIONS: Fatigue continues to be a problem for breast carcinoma survivors many years after cancer diagnosis, with 21% reporting persistent problems with fatigue. Several factors that may contribute to long-term fatigue are amenable to intervention, including depression and comorbid medical conditions.

Is tobacco use a problem among deaf college students?

College students' tobacco use poses a significant public health problem. Effective intervention requires understanding of this behavior among race/ethnic, cultural, and linguistic collegiate subgroups, including deaf and hard of hearing collegians. Findings from a first-ever tobacco-related survey among this understudied population are reported. The authors used written questionnaires and the Interactive Video Questionnaire, a multimedia computer technology developed for use with the deaf and hard of hearing, to interview 241 volunteers on seven California college campuses. They found lower self-reported current smoking prevalence (14.5%) relative to collegians in the general population, but considerable ever smoking (65.1%) and multiple types of tobacco use (37.3%). The authors report on factors associated with tobacco use and on students' exposure to cigarette marketing, gaps experienced in receipt of antitobacco messages and services, and students' antitobacco intervention recommendations. Limitations of the research are described, including possible underreporting of participants' tobacco use.

The BCPT symptom scales: a measure of physical symptoms for women diagnosed with or at risk for breast cancer.

BACKGROUND: Documentation of concurrent and late side effects of medical interventions to prevent and treat breast cancer is important in research and clinical practice. We used the Breast Cancer Prevention Trial (BCPT) Symptom Checklist to develop an instrument (BCPT Symptom Scales) that could be used to assess side effects and to examine correlates of the derived symptom dimensions among patient populations. METHODS: Exploratory and confirmatory factor analyses were conducted using data from the 42-item BCPT Symptom Checklist completed by four distinct patient populations (N = 2208) who had previously been diagnosed with breast cancer or were at risk for the disease. We examined associations among the resulting BCPT Symptom Scales and demographic and cancer-related variables and a widely used measure of health-related quality of life. RESULTS: Exploratory and confirmatory factor analyses revealed eight factors corresponding to physical symptoms associated with cancer treatment, chemoprevention, menopause, and normal aging: hot flashes, nausea, bladder control, vaginal problems, musculoskeletal pain, cognitive problems, weight problems, and arm problems. On the derived BCPT Symptom Scales, women reported somewhat higher mean scores on scales for hot flashes, pain, and weight problems than on scales for the other symptoms. Demographic and cancer-related variables accounted for up to 15% of the interindividual variance in how women responded to the symptom scales. The most consistent predictors of reporting greater symptoms included lower education level and previous receipt of chemotherapy. CONCLUSIONS: Meaningful symptom dimensions, identified across four samples of women, were associated with demographic and breast cancer-related variables. The BCPT Symptom Scales offer a valuable refinement of the original BCPT Symptom Checklist to assess side effects associated with the treatment and prevention of breast cancer.

Smoking prevalence and correlates among Chinese- and Filipino-American adults: findings from the 2001 California Health Interview Survey.

OBJECTIVES: We report prevalence rates and correlates of cigarette smoking among a population-based sample of Chinese- and Filipino-American adults together with rates found in other racial/ethnic groups in California. METHODS: All analyses are based on the 2001 California Health Interview Survey. RESULTS: The proportion of current smokers among males was lowest among Chinese Americans (14%), followed by Non-Hispanic Whites (19%), Hispanics (20%), African Americans (22%), Filipino Americans (24%), American Indians/Alaska Natives (29%), and Pacific Islanders (32%). The proportion of current smokers among females was lowest among Chinese Americans (6%), followed by Hispanics (8%), Filipino Americans (11%), Non-Hispanic Whites (17%), African Americans (20%), Pacific Islander (21%), and American Indians/Alaska Natives (32%). Smoking rates were higher among foreign-born versus U.S.-born Asian males. CHIS data show an opposite effect among Asian women: acculturation to the U.S. is associated with increased smoking prevalence rates. Multivariate analyses with Chinese and Filipino respondents showed that the likelihood of smoking varied among foreign-born versus U.S.-born men (OR 2.59 for Chinese, 1.42 for Filipino, 2.01 for all Asian men combined) and for foreign-born versus U.S.-born women (OR 0.41 for Chinese, 0.38 for Filipino, and 0.59 for all Asian women combined). CONCLUSION: Public health intervention efforts should take into account Asian ethnic subgroup, gender, and acculturation status in targeting high-risk smoking groups.

Perceptions of positive meaning and vulnerability following breast cancer: predictors and outcomes among long-term breast cancer survivors.

BACKGROUND: Survival rates for women with early-stage breast cancer have increased significantly in recent years. However, little is known about the long-term impact of the cancer experience on women's psychological functioning. Theoretical and descriptive accounts suggest that cancer may evoke both perceptions of vulnerability and positive meaning, with potentially different effects on mental health. PURPOSE: This study was designed to evaluate the prevalence and stability of these perceptions in a large sample of breast cancer survivors, to identify their antecedents, and to determine their impact on long-term adjustment. METHODS: Breast cancer survivors (N = 763) were assessed longitudinally at 1 to 5 years and 5 to 10 years postdiagnosis. Participants completed surveys assessing perceptions of positive meaning and vulnerability and standard measures of psychological adjustment and quality of life. RESULTS: The majority of women reported positive changes in outlook and priorities as well as feelings of vulnerability at both assessment points. Consistent with hypotheses, results showed that perceptions of positive meaning and vulnerability were positively correlated and were both associated with factors that increased the disruptiveness of the cancer experience. Vulnerability was strongly associated with negative affect, whereas meaning was associated with positive affect in cross-sectional and longitudinal analyses. CONCLUSIONS: Results suggest that a cancer diagnosis may lead to enduring feelings of vulnerability as well as positive changes in meaning; however, these perceptions have very different mental health correlates.