Copyright (c) 2009 All rights reserved. http://works.bepress.com/rbrookmeyer Recent documents in Ron Brookmeyer en-us Thu, 02 Jul 2009 12:30:55 PDT 3600 http://works.bepress.com/rbrookmeyer/30 http://works.bepress.com/rbrookmeyer/30 Wed, 01 Apr 2009 14:39:53 PDT Objective: To evaluate adjustment procedures that have been proposed to correct HIV incidence rates derived from cross-sectional surveys of biomarkers (BED). These procedures were motivated by some reports that the biomarker BED approach overestimates incidence when compared to cohort studies.Design: Considered the Hargrove and McDougal adjustment procedures that adjust biomarker estimates of HIV incidence rates for misclassification with respect to the timing of infections. Methods: Performed mathematical and statistical analysis of the adjustment formulas. Evaluated sources of error in cohort studies of incidence that could also explain discrepancies between cohort and biomarker estimates.Results: The McDougal adjustment has no net effect on the estimate of HIV incidence because false positives exactly counterbalance false negatives. The Hargrove adjustment has a mathematical error that can cause significant underestimation of HIV incidence rates especially if there is a large pool of prevalent long standing infections. Conclusion: The two adjustment procedures of biomarker incidence estimates evaluated here that purport to correct for misclassification, do not increase accuracy and in some situations can introduce significant bias. Instead, the accuracy of biomarker estimates can be increased through improvements in the estimates of the mean window period of the populations under study and the representativeness of the cross-sectional samples. Cohort estimates of incidence are also subject to important sources of error and should not blindly be considered the gold standard for assessing the validity of biomarker estimates. Ron Brookmeyer HIV/AIDS http://works.bepress.com/rbrookmeyer/29 http://works.bepress.com/rbrookmeyer/29 Sun, 28 Dec 2008 13:49:19 PST We evaluate the effects of herd immunity on the power of vaccine trials. We consider large-scale trials in which persons are individually randomized to either placebo or vaccine. We evaluate the adequacy of naive power calculations that ignore the effects of herd immunity such as those based on the comparison of two independent binomials. We developed a simulation design to evaluate the quantitative effects of herd immunity on power. The simulation design accounted for nonhomogeneous mixing. We found that naive power calculations that ignore the effects of herd immunity can seriously overestimate power. In fact, we found that as sample size increases it is possible for the power to actually decrease. The reason is that herd immunity reduces the overall number of infections. In the situations we considered, power may eventually begin to decrease once the proportion of the population enrolled in the trial exceeds about 25%. We discuss the findings in the context of a pneumococcal vaccine trial for children. Our results serve as a cautionary note that naive sample size calculations for larger scale vaccine trials that ignore the impact of herd immunity can yield underpowered studies. Simulations such as that suggested here can help alert investigators to situations where significant dilution of power could result from ignoring the effects of herd immunity.The article is dedicated to the memory of Blake Charvat Blake Charvat Public Health: General Methods http://works.bepress.com/rbrookmeyer/28 http://works.bepress.com/rbrookmeyer/28 Sun, 28 Dec 2008 12:28:32 PST Background The doubling time is the number of chronological years for the age-specific incidence rate to double in magnitude. Doubling times describe the rate of increase of the risk of Alzheimer's disease (AD) with advancing age. Estimates of doubling times of AD assist in understanding disease etiology and forecasting future disease prevalence. The objective of this study was to investigate regional and gender differences in the doubling of AD age-specific incidence rates.Methods We identified all studies in the peer review literature that reported age-specific incidence rates for AD. We modeled the logarithm of the incidence rate as a linear function of age. We used both fixed effects models and random effects models to account for interstudy variation.Results AD incidence rates exponentially increase with increasing age. The overall estimate of the doubling time was 5.5 years. The doubling times from studies performed in North America and Europe were 6.0 and 5.8, respectively; whereas the doubling times in all other parts of the world were 5.0. There was no significant geographic differences in doubling times (P = .3). Although the doubling times were slightly longer for men (6.5 years) than for women (5.4 years), the difference was not significant (P = .3).Conclusions Doubling times of AD incidence rates are not statistically significantly different among populations throughout the world. The risk of AD grows exponentially with age, doubling approximately every 5 to 6 years. Although the shapes of the incidence curves are similar, there is considerable variation in absolute incidence rates throughout the world. Currently, there are limited epidemiologic data at the oldest ages, and further study is needed to accurately define the incidence curve above age 90. Kathryn Ziegler-Graham Aging http://works.bepress.com/rbrookmeyer/27 http://works.bepress.com/rbrookmeyer/27 Fri, 05 Sep 2008 20:53:18 PDT The development of an human immunodeficiency virus (HIV) test that detects recent infection has enabled the U.S. Centers for Disease Control and Prevention (CDC) to estimate annual HIV incidence (number of new infections per year, not per person at risk) in the United States from data on new HIV and acquired immunodeficiency syndrome (AIDS) diagnoses reported to HIV/AIDS surveillance. We developed statistical procedures to estimate the probability that an infected person will be detected as recently infected, accounting for individuals choosing whether and how frequently to seek HIV testing, variation of testing frequency, the reporting of test results only for infected persons, and infected persons who never had an HIV-negative test. The incidence estimate is the number of persons detected as recently infected divided by the estimated probability of detection. We used simulation to show that, under the assumptions we make, our procedures have acceptable bias and correct confidence interval coverage. Because data on the biomarker for recent infection or on testing history were missing for many persons, we used multiple imputation to apply our models to surveillance data. CDC has used these procedures to estimate HIV incidence in the United States. John Karon HIV/AIDS http://works.bepress.com/rbrookmeyer/26 http://works.bepress.com/rbrookmeyer/26 Sun, 24 Aug 2008 20:15:38 PDT Background: Although the prevalence of dementia increases with age from ages 65 to 85, whether this increase continues after age 90 is unclear. Most studies reporting on dementia prevalence do not have sufficient participants to estimate prevalence for specific ages and sexes above age 90. Here, we estimate age- and sex-specific prevalence of all-cause dementia in the oldest-old, those aged 90 and older. Methods: Participants are 911 elderly from The 90+ Study, a population-based study of aging and dementia in people aged 90 and above. Dementia was diagnosed using in-person examinations as well as telephone and informant questionnaires. Results: The overall prevalence of all-cause dementia was higher in women (45%, 95% CI = 41.5-49.0) than men (28%, 95% CI = 21.7-34.2). Among women, prevalence increased with age after age 90, essentially doubling every 5 years. A lower prevalence of dementia was significantly associated with higher education in women but not in men. Conclusions: In a very large sample of participants aged 90 and older, prevalence of all-cause dementia doubled every 5 years for women but not men. Maria Corrada Aging http://works.bepress.com/rbrookmeyer/25 http://works.bepress.com/rbrookmeyer/25 Sun, 24 Aug 2008 20:09:55 PDT Context: Incidence of human immunodeficiency virus (HIV) in the United States has not been directly measured. New assays that differentiate recent vs long-standing HIV infections allow improved estimation of HIV incidence. Objective: To estimate HIV incidence in the United States. Design, Setting, and Patients : Remnant diagnostic serum specimens from patients 13 years or older and newly diagnosed with HIV during 2006 in 22 states were tested with the BED HIV-1 capture enzyme immunoassay to classify infections as recent or long-standing. Information on HIV cases was reported to the Centers for Disease Control and Prevention through June 2007. Incidence of HIV in the 22 states during 2006 was estimated using a statistical approach with adjustment for testing frequency and extrapolated to the United States. Results were corroborated with back-calculation of HIV incidence for 1977-2006 based on HIV diagnoses from 40 states and AIDS incidence from 50 states and the District of Columbia. Main Outcome Measure : Estimated HIV incidence. Results: An estimated 39 400 persons were diagnosed with HIV in 2006 in the 22 states. Of 6864 diagnostic specimens tested using the BED assay, 2133 (31%) were classified as recent infections. Based on extrapolations from these data, the estimated number of new infections for the United States in 2006 was 56 300 (95% confidence interval [CI], 48 200-64 500); the estimated incidence rate was 22.8 per 100 000 population (95% CI, 19.5-26.1). Forty-five percent of infections were among black individuals and 53% among men who have sex with men. The back-calculation (n = 1.230 million HIV/AIDS cases reported by the end of 2006) yielded an estimate of 55 400 (95% CI, 50 000-60 800) new infections per year for 2003-2006 and indicated that HIV incidence increased in the mid-1990s, then slightly declined after 1999 and has been stable thereafter. Conclusions: This study provides the first direct estimates of HIV incidence in the United States using laboratory technologies previously implemented only in clinic-based settings. New HIV infections in the United States remain concentrated among men who have sex with men and among black individuals. Irene Hall HIV/AIDS http://works.bepress.com/rbrookmeyer/24 http://works.bepress.com/rbrookmeyer/24 Fri, 21 Dec 2007 10:31:26 PST Mortality rate ratios and the associated proportional hazards models have been used to summarize the effect of Alzheimer's disease on longevity. However, the mortality rate ratios vary by age and therefore do not provide a simple parsimonious summary of the effect of the disease on lifespan. Instead, we propose a new parameter that is defined by an additive multistate model. The proposed multistate model accounts for different stages of disease progression. The underlying assumption of the model is that the effect of disease on mortality is to add a constant amount to death rates once the disease progresses from an early to late stage. We explored the properties of the proposed model; in particular the behavior of the mortality rate ratio and median survival that is induced by the model. We combined information from several data sources to estimate the parameter in our model. We found that the effect of Alzheimer's disease on longevity is to increase the absolute annual risk of death by about 8% once a person progressed to late stage disease. Most importantly, we find that this additive effect is the same regardless of the patients' age or gender. Thus, the proposed additive multi-state model provides a parsimonious and clinically interpretable description of the effects of Alzheimer's disease on mortality. Elizabeth Johnson Aging http://works.bepress.com/rbrookmeyer/23 http://works.bepress.com/rbrookmeyer/23 Thu, 11 Jan 2007 11:52:10 PST Background: The goal was to forecast the global burden of Alzheimer's disease and evaluate the potential impact of interventions that delay disease onset or progression. Methods: A stochastic multi-state model was used in conjunction with U.N. worldwide population forecasts and data from epidemiological studies on risks of Alzheimer's disease. Findings: In 2006 the worldwide prevalence of Alzheimer's disease was 26.6 million. By 2050, prevalence will quadruple by which time 1 in 85 persons worldwide will be living with the disease. We estimate about 43% of prevalent cases need a high level of care equivalent to that of a nursing home. If interventions could delay both disease onset and progression by a modest 1 year, there would be nearly 9.2 million fewer cases of disease in 2050 with nearly all the decline attributable to decreases in persons needing high level of care. Interpretation: We face a looming global epidemic of Alzheimer's disease as the world's population ages. Modest advances in therapeutic and preventive strategies that lead to even small delays in Alzheimer's onset and progression can significantly reduce the global burden of the disease. Ron Brookmeyer Aging http://works.bepress.com/rbrookmeyer/22 http://works.bepress.com/rbrookmeyer/22 Thu, 11 Jan 2007 11:32:46 PST The objective of this paper is to describe methods for estimating current incidence rates for human immunodeficiency virus (HIV) that account for follow-up bias. Follow-up bias arises when the incidence rate among individuals in a cohort who return for follow-up is different from the incidence rate among those who do not return. The methods are based on the use of early markers of HIV infection such as p24 antigen. The first method, called the cross-sectional method, uses only data collected at an initial base-line visit. The method does not require follow-up data but does require a priori knowledge of the mean duration of the marker. A confidence interval procedure is developed that accounts for uncertainty in the duration of the marker. The second method combines the base-line data from all individuals together with follow-up data from those individuals who return for follow-up. This method has the distinct advantage of not requiring prior information about the mean duration of the marker. Several confidence interval procedures for the incidence rate are compared by simulation. The methods are applied to a study in India to estimate current HIV incidence. These data suggest that the epidemic is growing rapidly in some subpopulations in India Ron Brookmeyer HIV/AIDS http://works.bepress.com/rbrookmeyer/21 http://works.bepress.com/rbrookmeyer/21 Tue, 09 Jan 2007 09:41:28 PST Software was developed to forecast the global burden of Alzheimer's disease and evaluate the potential impact of interventions that delay disease onset and progression. The output includes 50 year projections of Alzheimer's disease prevalence by stage of disease and region of the world. The methods are based on a stochastic multi-state model The software incorporates U.N. worldwide population forecasts and data from epidemiological studies on risks of Alzheimer's disease. The user can also supply their own population projections, and modify input parameters for the model including the disease incidence rates, effects of interventions on disease onset and progression, and stages of disease. The software is sufficiently flexible that it can also be applied to forecasting other diseases in elderly populations. Ron Brookmeyer Aging