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Biomedical subjects

R Brookmeyer

Publications and source records attributed to R Brookmeyer.

At least 55 records · Page 3Linked to original sources

Managed mental health care and patterns of inpatient utilization for treatment of affective disorders.

In this analysis we made use of a large data base of individuals insured by large American corporations to estimate the impact of managed care provision on hospital care for depression. Data on 6,348 individuals hospitalized for depression were examined to assess the effect of managed care techniques on the cost per episode and the likelihood of rehospitalization. Preadmission certification programs were found to lead to significant long- and short-run savings for payers.

Adult↗

Sources of variability in prevalence rates of Alzheimer's disease.

OBJECTIVE: To investigate potential methodological reasons for the differences in published Alzheimer's disease (AD) prevalence rates. BACKGROUND: Studies reporting prevalence rates of AD have been published worldwide. These rates differ considerably, but may greatly reflect methodological differences. METHODS: All studies published between 1984 and 1993 that reported age-specific AD rates and sample sizes were included. Logistic regression identified variables that contribute to the variation in rates. Estimates of extrabinomial variation were also calculated. RESULTS: Studies characterized by the following features yielded significantly higher rates: inclusion of mild cases, use of laboratory studies, ascertainment of a sample rather than the total population, inclusion of both urban and rural populations, non-use of computerized tomography (CT) scans, non-use of the Hachinski Ischemic Score, and no adjustment for false negatives. The odds of having AD increased 18% for every year of age. The variation in the age-specific prevalence rates of AD was approximately 15 times that expected by sampling variation. However, approximately 76% of this excess variation in rates could be accounted for by methodological differences. CONCLUSIONS: After accounting for age, much of the variability in prevalence rates of AD in the published literature may be explained by differences in methodology. Some unexplained variation in prevalence rates, however, still remains.

Age Factors↗

Reliability of the Blessed Telephone Information-Memory-Concentration Test.

In-person cognitive evaluations can be costly and labor intensive in geographically widespread populations. Reliable telephone instruments that screen for cognitive status would greatly facilitate epidemiologic and other longitudinal studies. We evaluated the reliability of the Blessed Information-Memory-Concentration (IMC) test when administered by telephone. Eighty-four subjects with a wide range of cognitive abilities were administered the Blessed IMC twice over a 3-week interval. Forty-nine of the subjects were administered the test both by telephone and in-person, and 35 of the subjects were tested twice by telephone. Spearman's rank correlation was used to compare scores of the different administrations (.96; P < .001) and to examine test-retest reliability (.96; P < .001). The Blessed Telephone IMC (TIMC) test exhibits excellent reliability both when compared to in-person administration as well as in test-retest results. The Blessed TIMC appears to be a practical instrument for population and longitudinal studies when in-person assessment is not feasible.

Aged↗

Statistical analysis of passive surveillance disease registry data.

Passive surveillance disease data involve a registry of individuals who are at risk of disease and who are not under active follow up. The most serious limitations with such data are incomplete ascertainment of cases of disease and little or no follow-up information on patient vital status. This paper considers whether it is possible to estimate disease risk from such data and, if not, what additional information is required. In general, relative risks based on passive surveillance data will be biased even under the assumption that the probability of disease reporting and the hazard of death from other causes are the same for all individuals in the registry. However if the disease is rare, this bias is negligible. Methods are developed for estimating absolute disease incidence rates by combining passive surveillance data with a cohort study. Analytic approaches are proposed for the situations when death rates from all other causes are known and also unknown, and it is found that there is little loss in efficiency even if death rates are not known. There are considerable gains in efficiency for estimating absolute disease incidence rates by supplementing a cohort study with passive surveillance registry data compared to using the cohort study alone, especially if the exposure is rare and the cohort study is small relative to the size of the registry. Intuitively, the cohort data provides information about absolute rates of disease, while the passive surveillance data provides information about relative risks. The methods are applied to a registry of patients with an artificial heart valve that is at risk of breaking.

Cohort Studies↗

An empirical Bayes approach to smoothing in backcalculation of HIV infection rates.

Backcalculation is a methodology to reconstruct the past human immunodeficiency virus (HIV) infection rates from the AIDS incidence data and incubation distribution by deconvolution. Smoothing has proved important in backcalculation, and a key question is how to choose the amount of smoothing. This paper proposes an empirical Bayes approach in which the smoothing parameter is estimated from the data. We introduce a family of priors that reflect the notion of closeness of neighboring infection rates. The variance parameter in the prior family plays the role of the smoothing parameter and is estimated by a method similar to the residual maximum likelihood in linear random effects model through an efficient EM (expectation/maximization) algorithm. A number of penalized likelihood functions that have been used in backcalculation have an empirical Bayes formulation. A bootstrap confidence interval for the infection rates is proposed. The methodology is illustrated with United States AIDS incidence data.

Acquired Immunodeficiency Syndrome↗

The evolution of virus diseases: their emergence, epidemicity, and control.

The evolution of virus diseases, both their emergence and disappearance, involves complex interactions between the agent, the host, and the environment. These themes are illustrated by three examples, poliomyelitis of humans, bovine spongiform encephalopathy of cattle, and AIDS of humans. Emergence may be due to evolution of the virus genome, such as probably occurred in parvovirus infection of dogs and human immunodeficiency virus infection of humans. However, emergence of some new viral diseases can be traced to host or environmental factors with no change in the agent. Poliomyelitis, an enteric infection, probably emerged as an epidemic disease due to improvements in personal hygiene and public sanitation which led to a delay in the occurrence of initial infections from the perinatal period (when maternal antibody protected against paralysis) to later childhood when passive immunity had waned. Bovine spongiform encephalopathy is a common source epidemic which was transmitted through nutritional supplements which became contaminated due to a change in the method of production of bone meal supplements in rendering plants. The reduction of disappearance of virus diseases usually involves human intervention, as exemplified by immunization for smallpox and other virus diseases of humans and animals. Naturally occurring immunity may lead to fadeout of a virus as seen with measles in isolated island populations. Evolution of a virus can also result in waning of a disease as seen with myxomatosis among rabbits in Australia. The evolution of virus diseases is a provocative scientific topic and carries lessons relevant to the control of important diseases of humans, animals, and plants.

Acquired Immunodeficiency Syndrome↗

Analysis of infectious disease data from partner studies with unknown source of infection.

Partner studies are useful for estimating the transmission probabilities of infectious diseases. However, it is often not known which partner was the source of the infection (the index case). The objective of this paper is to develop statistical methods for analyzing partner studies when it is uncertain which partners acquired the infection from sources outside the partnership. The approach involves simultaneously modelling the probability of acquisition of infection from outside the partnership, and the probability of transmission within the partnership as a function of covariates. An EM algorithm is presented. Efficiency and simulation results are given in some special situations involving heterosexual transmission studies. In heterosexual partner studies, the methods depend crucially on the availability of a covariate that provides information about which partner was the likely source of infection.

Algorithms↗

Statistical models for prevalent cohort data.

In prospective cohort studies individuals are sometimes recruited according to a certain cross-sectional sampling criterion. A prevalent cohort is defined as a group of individuals who have a certain disease at enrollment into the study. Statistical models for the analysis of prevalent cohort data are considered when the onset or diagnosis time of the disease is known. The incident proportional hazards model, where the time scale is duration with disease, is compared to the prevalent proportional hazards model, where the fundamental time scale is follow-up time. In certain cases the time of enrollment may coincide with another event (such as the initiation of treatment). This situation is also considered and its limitations highlighted. To illustrate the methodological ideas discussed in the paper, the analysis of data from an observational study of zidovudine (ZVD) in patients with the acquired immunodeficiency syndrome (AIDS) is presented.

Acquired Immunodeficiency Syndrome↗

Projections of the number of persons diagnosed with AIDS and the number of immunosuppressed HIV-infected persons--United States, 1992-1994.

This report presents projections of the number of persons who will initially be diagnosed with a condition included in the 1987 surveillance definition for acquired immunodeficiency syndrome (AIDS) in the United States during the period 1992-1994. The report also presents estimates and projections of the prevalence of persons infected with the human immunodeficiency virus (HIV) who have CD4+ T-lymphocyte (T-cell) counts < 200/microL and who have not been diagnosed with a condition listed in the 1987 AIDS surveillance definition. These estimates and projections are used to predict the effect of expanding the AIDS surveillance definition to include all HIV-infected persons with a CD4+ T-cell count < 200/microL. Approximately 58,000 persons were diagnosed with AIDS in the United States during 1991. During the period 1992-1994, the number of persons newly diagnosed with AIDS is expected to increase by at most a few percent annually, with approximately 60,000-70,000 persons diagnosed per year. Although AIDS diagnoses among homosexual and bisexual men and among injecting drug users are projected to reach a plateau during this period, the number of AIDS diagnoses among persons whose HIV infection is attributed to heterosexual transmission of HIV is likely to continue to increase through 1994. The number of living persons who have been diagnosed with AIDS is expected to increase from approximately 90,000 in January 1992 to approximately 120,000 in January 1995. There is, however, considerable uncertainty in these projections. For example, the plausible range for the number of persons initially diagnosed with AIDS in 1994 is 43,000-93,000. CDC estimates that, as of January 1992, 115,000-170,000 U.S. residents had severe immunosuppression (a CD4+ T-cell count < 200 cells/microL without a diagnosis of AIDS in an HIV-infected person). Only about 50,000 of these persons were receiving medical care for HIV-related conditions and were known to have a CD4+ T-cell count < 200 cells/microL. The number of persons with severe immunosuppression is expected to increase to 130,000-205,000 by January 1995, with the actual number more likely to be in the lower half of this range than the upper half. The expanded AIDS surveillance definition, which includes severe immunosuppression, is predicted to result in an increase of approximately 75% in the number of persons reported during 1993, but an increase of < 20% in 1994 compared with the number of persons who would have been reported had the definition not been changed.(ABSTRACT TRUNCATED AT 400 WORDS)

Acquired Immunodeficiency Syndrome↗

Effects of mid-point imputation on the analysis of doubly censored data.

Doubly censored data arise in some cohort studies of the AIDS incubation period because the time of infection may be known only up to an interval defined by two successive screening tests for HIV antibody. A simple analytic approach is to impute the infection time by the mid-point of the interval and then apply standard survival techniques for right censored data. The objective of this paper is to investigate the statistical properties of such a mid-point imputation approach. We investigated the asymptotic bias of the Kaplan-Meier estimate, coverage probabilities of associated confidence intervals, bias in hazard ratio, and the size of the logrank test. We show that the statistical properties of mid-point imputation depend strongly on the underlying distributions of infection times and the incubation periods, and the width of the interval between screening tests. In the absence of treatment, the median incubation period of HIV infection is approximately 10 years, and we conclude that, for this situation, mid-point imputation is a reasonable procedure for interval widths of 2 years or less.

Bias↗

Interpartner reliability of reporting of recent sexual behaviors.

Epidemiologic studies exploring risks for sexually transmitted diseases, including human immunodeficiency virus infection, typically rely on self-report of sexual behaviors. Estimates of the incidence and prevalence of sexual practices are important measures for assessment of behavioral interventions as well as for examining disease transmission. This study examined the degree of agreement within heterosexual couples reporting frequency and type of sexual behaviors, including condom use. Self-reports were obtained from 71 couples attending Baltimore sexually transmitted disease clinics in 1989-1990 regarding the number of days and number of episodes of three specific sexual practices (any type of sexual activity, vaginal sex, and vaginal sex with condom use) over a 30-day period. Paired t test analysis revealed both sexes to be very consistent in their reporting of recent sexual experiences. Multivariate analysis showed that agreement did not vary by socioeconomic status, by whether the partners were married to each other, or by age. These findings suggest that reliable information regarding sexual behaviors may be obtained from men or women.

Adult↗

Reconstruction and future trends of the AIDS epidemic in the United States.

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. Due both to the decline in the underlying infection rate and to the development of effective therapies that may delay AIDS diagnosis, overall AIDS incidence may plateau during the next 5 years. However, the number of individuals with advanced HIV disease without a diagnosis of AIDS who could potentially benefit from therapy is expected to increase 40% by 1995 as infected individuals progress to more advanced stages of HIV disease. Thus, although the overall HIV infection rate has declined, the demands on the U.S. health care system for treatment and care of HIV-infected individuals remain enormous.

Acquired Immunodeficiency Syndrome↗

Relationship of serum copper and zinc levels to HIV-1 seropositivity and progression to AIDS.

Dietary, serum, and tissue levels of copper and zinc were determined at baseline in a cohort of homosexual men to investigate the relationship of these factors to human immunodeficiency virus type 1 (HIV-1) seropositivity and subsequent progression to AIDS. Using a nested case control design, 54 asymptomatic HIV-1 seropositives who later progressed to AIDS were compared with 54 HIV-1 seropositives who did not progress and 54 seronegatives (mean follow-up time 2.5 years). Serum levels of copper and zinc were estimated from frozen serum samples, tissue levels from stored toenail samples, and dietary intakes from a semiquantitative food frequency questionnaire administered at baseline. Neither dietary copper and zinc nor their levels in toenails were associated with HIV-1 seropositivity or progression to AIDS. However, serum copper levels were higher (p = 0.002) in HIV-1-seropositive progressors (mean = 115.6 micrograms/dl; SD = 17.1) than the seropositive nonprogressors (mean = 109.0 micrograms/dl; SD = 15.8) and the seronegatives (mean = 101.9 micrograms/dl; SD = 16.7). Conversely, serum zinc levels were lower (p = 0.016) in the seropositive progressors (mean = 85.2 micrograms/dl; SD = 11.5) than the seropositive nonprogressors (mean = 90.7 micrograms/dl; SD = 12.0) and the seronegatives (mean = 92.0 micrograms/dl; SD = 14.7). Furthermore, in a logistic regression, higher serum copper (odds ratio per 20-micrograms/dl increase = 2.23; 95% confidence interval = 1.02-4.87) and lower serum zinc (odds ratio per 20-micrograms/dl increase = 0.30; 95% confidence interval = 0.14-0.66) predicted progression to AIDS independently of baseline CD4+ lymphocyte level, age, and calorie-adjusted dietary intakes of both nutrients.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗

The analysis of delays in disease reporting: methods and results for the acquired immunodeficiency syndrome.

In order to monitor accurately trends in disease incidence, it is necessary to account for delays in the reporting of cases to central registries. The objective of the paper is to develop simple methods for the analysis of reporting delays in order to identify the main sources of heterogeneity and to adjust reported disease incidence data. The analysis is complicated because the data are right truncated. A simple and flexible method for the regression analysis of reporting delays is proposed, which can be easily implemented with standard computing tools for generalized linear models or logistic regression. The method was used to analyze delays in reporting the acquired immunodeficiency syndrome in the United States among cases who met the pre-1987 surveillance definition. This analysis showed significant geographic variation. Delays were shortest in the Northeast and longest in the South. The influences of risk groups and calendar year of diagnosis were not consistent across each of the geographic regions. Variation among risk groups was attributed primarily to slower reporting of transfusion-associated and pediatric acquired immunodeficiency syndrome cases. An overall trend toward longer delays with calendar time of diagnosis was attributed primarily to a trend toward longer delays in the Northeast. These methods and results are useful both for the evaluation of surveillance procedures in order to improve disease reporting and for adjustment of disease incidence data.

Acquired Immunodeficiency Syndrome↗

Statistical problems in epidemiologic studies of the natural history of disease.

The development of effective disease prevention and treatment programs depends on an understanding of the natural history of disease. A conceptual framework is presented for disease natural history and consists of an asymptomatic period of disease followed by a period of symptomatic disease. The focus is on epidemiologic studies for identifying risk factors of the onset of asymptomatic disease, for identifying cofactors of progression to symptomatic disease, and for estimating the duration of the asymptomatic period. The strengths and limitations of various epidemiologic study designs and sources of epidemiologic data are considered for characterizing disease natural history. Issues in the interpretation and analysis of natural history parameters of disease estimated from cross-sectional, prevalent cohort, cohort, and matched case-control studies are considered. The issues and analytic methods are illustrated with studies of the acquired immunodeficiency syndrome (AIDS) and cervical cancer. Based on these analytic methods, an estimate of the incubation period distribution of AIDS is given.

Acquired Immunodeficiency Syndrome↗

Statistical modelling of the AIDS epidemic for forecasting health care needs.

The objective of this paper is to develop statistical methods for estimating current and future numbers of individuals in different stages of the natural history of the human immunodeficiency (AIDS) virus infection and to evaluate the impact of therapeutic advances on these numbers. The approach is to extend the method of back-calculation to allow for a multistage model of natural history and to permit the hazard functions of progression from one stage to the next to depend on calendar time. Quasi-likelihood estimates of key quantities for evaluating health care needs can be obtained through iteratively reweighted least squares under weakly parametric models for the infection rate. An approach is proposed for incorporating into the analysis independent estimates of human immunodeficiency virus (HIV) prevalence obtained from epidemiologic surveys. The methods are applied to the AIDS epidemic in the United States. Short-term projections are given of both AIDS incidence and the numbers of HIV-infected AIDS-free individuals with CD4 cell depletion. The impact of therapeutic advances on these numbers is evaluated using a change-point hazard model. A number of important sources of uncertainty must be considered when interpreting the results, including uncertainties in the specified hazard functions of disease progression, in the parametric model for the infection rate, in the AIDS incidence data, in the efficacy of treatment, and in the proportions of HIV-infected individuals receiving treatment.

Acquired Immunodeficiency Syndrome↗