A simple genetic stratification method for lower cost, more expedient clinical trials in early Alzheimer's disease: A preliminary study of tau PET and cognitive outcomes.

INTRODUCTION: Identifying individuals who are most likely to accumulate tau and exhibit cognitive decline is critical for Alzheimer's disease (AD) clinical trials. METHODS: Participants (N = 235) who were cognitively normal or with mild cognitive impairment from the Alzheimer's Disease Neuroimaging Initiative were stratified by a cutoff on the polygenic hazard score (PHS) at 65th percentile (above as high-risk group and below as low-risk group). We evaluated the associations between the PHS risk groups and tau positron emission tomography and cognitive decline, respectively. Power analyses estimated the sample size needed for clinical trials to detect differences in tau accumulation or cognitive change. RESULTS: The high-risk group showed faster tau accumulation and cognitive decline. Clinical trials using the high-risk group would require a fraction of the sample size as trials without this inclusion criterion. DISCUSSION: Incorporating a PHS inclusion criterion represents a low-cost and accessible way to identify potential participants for AD clinical trials.

The differential associations of preexisting conditions with trauma-related outcomes in the presence of competing risks.

INTRODUCTION: Pre-existing chronic conditions (PECs) pose a unique problem for the care of aging trauma populations. However, the relationships between specific conditions and outcomes after injury are relatively unknown. Evaluation of trauma patients is further complicated by their discharge to care facilities, where mortality risk remains high. Traditional approaches for evaluating in-hospital mortality do not account for the discharge of at-risk patients, which constitutes a competing risk event to death. The objective of this study was to evaluate associations between 40 PECs and two clinical outcomes in the context of competing risks among older trauma patients. METHODS: This retrospective study evaluated blunt-injured patients aged 55 years and older admitted to a level I trauma centre in 2006-2012. Outcomes were hospital length of stay (HLOS) and in-hospital mortality. Survivors were classified as discharges home or discharges to care facilities. Competing risks regression was used to evaluate each PEC with in-hospital mortality, accounting for discharges to care facilities as competing events. Competing risk estimates were compared to Cox model estimates, for which all survivors to discharge were non-events. Analyses were stratified using injury-based mortality risk at a 50% cutpoint (high versus low). RESULTS: Among 4653 patients, 176 died in-hospital, 3059 were discharged home, and 1418 were discharged to a care facility. Most patients (98%) were classified with a low mortality risk. Only haemophilia and coagulopathy were consistently associated with longer HLOS. In the low-risk subgroup, in-hospital mortality was most strongly associated with liver diseases, haemophilia, and coagulopathy. In the high-risk group, Parkinson's disease, depression, and cancers showed the strongest associations. Accounting for the competing event altered estimates for 12 of 19 significant conditions. CONCLUSIONS: Excess mortality among patients expected to survive their injuries may be attributable to complications resulting from PECs. Discharges to care facilities constitute a bias in the evaluation of in-hospital mortality and should be considered for the accurate calculation of risk. In conjunction with injury measures, consideration of PECs provides physicians with a foundation to plan clinical decisions in older trauma patients.

Smoking ban policies and their influence on smoking behaviors among current California smokers: a population-based study.

OBJECTIVE: To assess whether smoking ban policies are associated with smoking reduction and quit attempts among California smokers. METHODS: Data were examined for 1718 current smokers from follow-up telephone interviews conducted in 2011 of persons previously identified as smokers in a representative sample of the adult population of California. Population weighted logistic regressions controlling for demographic and other variables were used to evaluate the association between smoking ban policies (home, work, and town) and changes in tobacco use (past year quit attempt or reduction in smoking rate). RESULTS: Living in a home with a total ban was significantly associated with smoking reduction (adjusted odds ratio, AOR: 2.4, 95% CI: 1.4-4.2) and making a quit attempt (AOR: 2.3, 95% CI: 1.3-3.9) compared to living in a home with no home ban. Self-reported perception of an outdoor ban in one's city/town was associated with smoking reduction (AOR: 1.7, 95% CI: 1.02-2.7) and making a quit attempt (AOR: 1.8, 95% CI: 1.05-2.9). CONCLUSION: These results indicate that smoking bans not only protect nonsmokers from the harms of secondhand smoke, but are also associated with smoking reduction and cessation.

Perceived price sensitivity by ethnicity and smoking frequency among California Hispanic and non-Hispanic white smokers.

OBJECTIVES: Little is currently known about price sensitivity across ethnic groups as well as for non-daily smokers. To address this issue, this study compared perceived price sensitivity across smoking status (daily and non-daily) and within ethnicity (Hispanic and non-Hispanic White) in a recent representative population survey of California smokers. METHODS: This study employed data from the 2008 California Tobacco Survey (CTS), a large population-based random-digit-dialed telephone survey. Participants were 1,777 non-Hispanic White and 450 Hispanic respondents who had smoked at least 100 cigarettes and currently smoked daily or on some days. RESULTS: Differences in perceived price sensitivity were found by ethnicity when controlling for age, gender, and cigarette consumption. Comparisons across ethnic groups indicated that Hispanic smokers, in general, have more price-sensitive perceptions than non-Hispanic White smokers. However, daily versus non-daily status had no effect on price sensitivity when controlling for cigarette quantity. CONCLUSIONS: These findings indicate that pricing increases may be differentially influential for Hispanic compared with non-Hispanic White smokers across smoking status categories.

Increasing hookah use in California.

Hookah use is gaining popularity nationwide. We determined the correlates and trends for hookah use from the California Tobacco Survey. Between 2005 and 2008 hookah use increased more than 40%, and in 2008, 24.5% of young men reported ever using a hookah. Hookah use was more common among the young (18-24 years), the educated, the non-Hispanic Whites, and the cigarette smokers. Hookah use is increasing in California, especially among young adults, and in 2008 reached the highest prevalence ever reported for both genders.

The net effect of alternative allocation ratios on recruitment time and trial cost.

BACKGROUND: Increasing the proportion of subjects allocated to the experimental treatment in controlled clinical trials is often advocated as a method of increasing recruitment rates and improving the performance of trials. The presumption is that the higher likelihood of randomization to the experimental treatment will be perceived by potential study enrollees as an added benefit of participation and will increase recruitment rates and speed the completion of trials. However, studies with alternative allocation ratios require a larger sample size to maintain statistical power, which may result in a net increase in time required to complete recruitment and a net increase in total trial cost. PURPOSE: To describe the potential net effect of alternative allocation ratios on recruitment time and trial cost. METHODS: Models of recruitment time and trial cost were developed and used to compare trials with 1:1 allocation to trials with alternative allocation ratios under a range of per subject costs, per day costs, and enrollment rates. RESULTS: In regard to time required to complete recruitment, alternative allocation ratios are net beneficial if the recruitment rate improves by more than about 4% for trials with a 1.5:1 allocation ratio and 12% for trials with a 2:1 allocation ratio. More substantial improvements in recruitment rate, 13 and 47% respectively for scenarios we considered, are required for alternative allocation to be net beneficial in terms of tangible monetary cost. LIMITATIONS: The cost models were developed expressly for trials comparing proportions or means across treatment groups. CONCLUSIONS: Using alternative allocation ratio designs to improve recruitment may or may not be time and cost-effective. Using alternative allocation for this purpose should only be considered for trial contexts where there is both clear evidence that the alternative design does improve recruitment rates and the attained time or cost efficiency justifies the added study subject burden implied by a larger sample size.

ADCS Prevention Instrument Project: overview and initial results.

One objective of the Alzheimer's Disease Cooperative Study (ADCS) is to develop new or improved instruments and assessment methods for evaluating treatment efficacy in Alzheimer disease (AD) clinical trials. The ADCS Instrument Committee has previously helped to define the state of the art in assessment for AD and Mild Cognitive Impairment clinical trials. We are now entering an exciting era of primary prevention trials to evaluate promising treatments that may delay disease onset and there is a need to develop appropriate instruments for these trials. The ADCS instrument committee has undertaken a project to develop instruments for prevention studies that assess domains known to be important in AD. Prevention trials are long and require large numbers of subjects, making them costly and requiring a high burden of participation for subjects. The current study focused on developing instruments that can be completed at home and in the clinic. The instruments are being evaluated in a cohort of nondemented elderly participating in a 4-year longitudinal study that simulates the design of a primary prevention trial. This report describes the design, baseline characteristics, and some longitudinal outcomes of the study cohort through the completion of the first 2 years of follow-up. We also describe the assessment domains to be measured with our new experimental instruments. This study recruited 644 subjects, 75 years of age and older. Participation in a "book club" that provided free books of interest to elders was offered as a recruitment incentive. Approximately 23% had some mild cognitive symptoms consistent with a Clinical Dementia Rating of 0.5. All subjects received a standardized in-clinic evaluation at baseline, which is repeated annually for 4 years to identify cases suspected of developing dementia and to measure longitudinal change on established clinical assessments. Subjects completed a set of self-administered experimental instruments at home or in the clinic designed to assess cognitive function and behavior, global change, activities of daily living, quality of life, and resource use. An additional "mail-in cognitive function questionnaire" was obtained separately by mail, 1 month before the other assessments. To evaluate the feasibility, efficiency, and validity of the home-based instruments in comparison with acquiring the same information during a clinic visit, subjects were randomized to 1 of 2 conditions in which the baseline and annual follow-up assessments are completed either at home ("home group") or at the study site during their clinic visits ("clinic group"). This initial report describes the ongoing 4-year longitudinal study and provides baseline results, which confirm the feasibility of obtaining home-based clinical information via mail or telephone. Initial results for the experimental instruments and for the book club are reported in separate accompanying articles.

ADCS Prevention Instrument Project: assessment of instrumental activities of daily living for community-dwelling elderly individuals in dementia prevention clinical trials.

BACKGROUND: In primary prevention trials for Alzheimer disease, the inception cohort typically has normal or minimally impaired complex activities of daily living (ADL). ADL change during a trial could trigger detailed evaluation or serve as an outcome measure. A brief, easily administered, and reliable ADL rating scale would assist prevention studies. OBJECTIVES: To develop an ADL scale for prevention trials that allows self-rating or completion by informants. METHODS: The Activities of Daily Living-Prevention Instrument (ADL-PI) was developed, comprising 15 ADL and 5 physical function questions. Six hundred forty-four elderly subjects participating in the Prevention Instrument Project completed a self-rated version of the ADL-PI, and informants for 632 subjects completed an informant version. Informants also completed a Mild Cognitive Impairment (MCI) ADL questionnaire to allow comparisons. RESULTS: Subjects performed well on all ADL scales at baseline. Completion of the ADL-PI questionnaires at home or in-clinic yielded comparable information. Scores from baseline to 3 months had good reliability. The ADL-PI, obtained from either self-report or informants, discriminated between subjects rated as CDR 0 and CDR 0.5. Subjects with worse baseline cognitive performance also had slightly worse ADL-PI scores. Preliminary analysis indicates that subjects who triggered cognitive evaluations had slightly lower baseline ADL-PI scores by both self and informant reports. CONCLUSIONS: The ADL-PI can be completed at home or in clinic, and has adequate reliability. The utility of self-administered and informant versions and predictive value of reported deficits requires further follow-up.

ADCS Prevention Instrument Project: quality of life assessment (QOL).

Information about quality of life (QOL) is valuable in evaluating pharmaceutical agents but it is not adequately assessed in many dementia drug trials. In prevention trials, following participants to conversion to AD requires QOL scales appropriate for both normal and cognitively impaired individuals. Our objective was to evaluate the utility of several scales for subject or informant QOL assessment: Quality of Life-AD; Quality of Life Activity Inventory; SF-36; SF-12 (a shortened version of the SF-36); and Satisfaction with Life Scale. Measurements were collected from 644 subject-study partner pairs, half of whom completed the instruments at the clinic and half at home. Three-month test-retest data were collected. Scales administered at home or in clinic did not differ significantly. Subject self-ratings showed a wide range for all scales. Test-retest intraclass coefficients ranged from 0.67 to 0.77. Moderately high interscale associations suggest that the scales are measuring common aspects of QOL but are not equivalent. Furthermore, they differed with respect to associations with demographic variables and QOL determinants. We conclude that the QOL scores at baseline show sufficient range and reliability to suggest they will have utility in tracking QOL through conversion to dementia.

ADCS Prevention Instrument Project: pharmacoeconomics: assessing health-related resource use among healthy elderly.

BACKGROUND: The Prevention Instrument project of the Alzheimer's Disease Cooperative Study (ADCS) seeks to develop instruments to assess treatment efficacy including potential economic benefit. The Resource Use Inventory (RUI) is an instrument that has been used to capture resource utilization and costs in populations with Alzheimer disease (AD). However, resource utilization and costs for healthy, cognitively intact elderly as they begin to demonstrate cognitive deterioration are not well understood. In addition, the loss that relates to the subjects' own time as they transition through cognitive impairment is not well documented. OBJECTIVES: To evaluate the utility of the RUI in a sample of cognitively intact elderly individuals living in the community and enrolled in AD prevention trials. METHODS: The RUI was administered to 644 subjects and their study partners either at home or in the clinic. For half of each sample, 3-month retesting was carried out. The RUI consisted of 9 questions. The first part of the RUI captured subjects' use of direct medical care (eg, hospitalizations) and nonmedical care (eg, home health aides). The second part of the RUI captured the time caregivers spend providing care to the subjects. The third part of the RUI captured subjects' participation in volunteer work and employment. The assessment interval for each question was the past 3 months. RESULTS: The percentage of RUI forms returned incomplete or inaccurate for both in-clinic and at-home groups was extremely low. There were no differences in utilization rates between in-clinic and at-home group for all items in the RUI. Except for use of outpatient procedures, tests, or treatments, there were no differences in utilization rates between subjects who filled out the RUI with the help of their study partners or by themselves. Items in the RUI were sensitive to subjects' cognitive and functional status and demographic characteristics. CONCLUSIONS: Home-based completion of the RUI by participants in an AD prevention study is feasible, and seems to provide data that are reliable and valid. The instrument will be useful for tracking resource and time use through transition from healthy to cognitive impairment.