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.

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.

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.

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.

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.

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.

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.

Primary care provider perceptions of barriers to and facilitators of colorectal cancer screening in a managed care setting.

BACKGROUND: Colorectal cancer (CRC) screening tests (e.g., fecal occult blood testing [FOBT], flexible sigmoidoscopy [FS], etc.) are underused. Primary care providers (PCPs) play a critical role in screening, but barriers to and facilitators of screening as perceived by PCPs in managed care settings are poorly understood. The objectives of the current study were to describe current CRC screening practices and to explore determinants of test use by PCPs in a managed care setting. METHODS: In 2000, a self-administered survey was mailed to a stratified, random sample of 1340 PCPs in a large, network model health maintenance organization in California. RESULTS: The survey response rate was 67%. PCPs indicated that 79% of their standard-risk patients were screened for CRC. PCP-reported median rates of recommendation for the use of specific screening tests were 90% for FOBT and 70% for FS. In logistic regression models, perceived barriers to the use of FOBT and FS included patient characteristics (e.g., education) and PCP-related barriers (e.g., failure to recall that patients were due for testing). Perceived facilitators of the use of FOBT and FS included interventions targeting certain aspects of the health care system (e.g., reimbursement) and interventions targeting certain aspects of the tests themselves (e.g., provision of evidence of a test's effectiveness). Assignment of high priority to screening, integrated medical group (as opposed to independent practice association) affiliation, and the proportion of patients receiving routine health maintenance examinations were positively associated with reported test use. CONCLUSIONS: CRC screening tests appear to be underused in the managed care setting examined in the current study. The perceived barriers and facilitators that were identified can be used to guide interventions aimed at increasing recommendations for, as well as actual performance of, CRC screening.

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.