Medical Biomathematics and Biometrics Commons^™

Worldwide Variation In The Doubling Time Of Alzheimer's Disease Incidence Rates, Kathryn Ziegler-Graham, Ron Brookmeyer, Elizabeth Johnson, H. Michael Arrighi

Ron Brookmeyer

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 …

Bayesian Identification, Selection And Estimation Of Functions In High-Dimensional Additive Models, Anastasios Panagiotelis, Michael Smith

Michael Stanley Smith

In this paper we propose an approach to both estimate and select unknown smooth functions in an additive model with potentially many functions. Each function is written as a linear combination of basis terms, with coefficients regularized by a proper linearly constrained Gaussian prior. Given any potentially rank deficient prior precision matrix, we show how to derive linear constraints so that the corresponding effect is identified in the additive model. This allows for the use of a wide range of bases and precision matrices in priors for regularization. By introducing indicator variables, each constrained Gaussian prior is augmented with a …

Confidence Intervals For Biomarker-Based Human Immunodeficiecny Virus Incidence Estimates And Differences Using Prevalent Data, Ron Brookmeyer, S Cole, H Chu

Ron Brookmeyer

Prevalent biological specimens can be used to estimate human immunodeficiency virus (HIV) incidence using a two-stage immunologic testing algorithm that hinges on the average time, say T, between testing HIV positive on highly and less sensitive enzyme immunoassays. Common approaches to confidence interval (CI) estimation for this incidence measure have included (1) ignoring the random error in T or (2) employing a Bonferroni adjustment to the box method. The authors present alternative Monte Carlo-based CIs for this incidence measure, as well as CIs for the biomarker-based incidence difference; standard approaches to CIs are typically appropriate for the incidence ratio. Using …

Modeling The Optimum Duration Of Antibiotic Prophylaxis In An Anthrax Outbreak, Ron Brookmeyer, Elizabeth Johnson, Robert Bollinger

Ron Brookmeyer

A critical consideration in effective and measured public health responses to an outbreak of inhalational anthrax is the optimum duration of antibiotic prophylaxis. We develop a competing-risks model to address the duration of antibiotic prophylaxis and the incubation period that accounts for the risks of spore germination and spore clearance. The model predicts the incubation period distribution, which is confirmed by empirical data. The optimum duration of antibiotic prophylaxis depends critically on the dose of inhaled spores. At high doses, we show that exposed persons would need to remain on antibiotic prophylaxis for at least 4 months, and considerable morbidity …

Statistical Models And Bioterrorism: Application To The U.S. Anthrax Outbreak, Ron Brookmeyer, Natalie Blades

Ron Brookmeyer

In the fall of 2001 an outbreak of inhalational anthrax occurred in the United States that was the result of bioterrorism. Letters contaminated with anthrax spores were sent through the postal system. In response to the outbreak, public health officials treated over 10,000 persons with antibiotic prophylaxis in the hopes of preventing further morbidity and mortality. No persons receiving the antibiotics subsequently developed disease. The question arises as to how many cases of disease may actually have been prevented by the public health intervention of antibiotic prophylaxis. A statistical model is developed to answer this question by relating to the …

Prevention Of Inhalational Anthrax In The U.S. Outbreak, Ron Brookmeyer, Natalie Blades

Ron Brookmeyer

No abstract provided.

Aids Epidemiology: A Quantitative Approach, Ron Brookmeyer, Mitchell Gail

Ron Brookmeyer

This comprehensive work confronts the problems that are unique to AIDS research and unites them under a single conceptual framework. It focuses on methods for the design and analysis of epidemiologic studies, the natural history of AIDS and the transmission of HIV, methods for tracking and projecting the course of the epidemic, and statistical issues in therapeutic trials. The various methods of monitoring and forecasting this disease receive comprehensive treatment. These methods include back-calculation, which the authors developed; interpretation of survey data on HIV prevalence; mathematical models for HIV transmission; and approaches that combine different types of epidemiological data. Much …

Reconstruction And Future Trends Of The Aids Epidemic In The United States, Ron Brookmeyer

Ron Brookmeyer

There has been considerable uncertainty in estimates of past and current human immunodeficiency virus (HIV) infection rates in the United States. Statistical estimates of historical infection rates can be obtained from acquired immunodeficiency syndrome (AIDS) incidence data and the incubation period. However, this approach is subject to a number of sources of uncertainty and two other approaches, epidemic models of HIV transmission and surveys of HIV prevalence, are used to corroborate and refine the statistical estimates. Analyses suggest the HIV infection rate in the United States grew rapidly in the early 1980s, peaked in the mid-1980s, and subsequently declined markedly. …

The Minimum Size Of The Aids Epidemic In The United States, Ron Brookmeyer, Mitchell Gail

Ron Brookmeyer

A new method based on the reported incubation period of transfusion-associated AIDS was used to estimate the number of AIDS cases likely to arise in the USA among those infected before 1986. Between 1986 and 1991 102 000 new cases are projected, with a total cumulative incidence of 135 000 AIDS cases. These estimates do not account for new infections after 1985 nor very long incubation periods and are thus the smallest numbers to be expected. Even if new infections can be effectively prevented, the epidemic will be five times larger than the number of cases observed so far.