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R Brookmeyer

Publications and source records attributed to R Brookmeyer.

At least 55 records · Page 3Linked to original sources

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

Simulation of Huntington's disease onset.

Previous investigators have noted that the type of sampling scheme used to study the natural history of Huntington's disease can affect the observed age of onset distribution. Simulated data are presented to demonstrate that bias is introduced when onset characteristics derived from prevalence samples (i.e., samples of affected individuals alive in the population) are used to evaluate cofactors of disease onset and to compute genetic risk estimates for persons "at risk" of developing the disease. This study demonstrates that prevalence sampling underestimates the proportion of Huntington's disease cases in the population with later onset ages. Using plausible values for onset time, duration, and life expectancy, simulation results suggest that the paternal transmission effect on Huntington's disease onset is overestimated when based on prevalence data.

Adolescent

Statistical methods for short-term projections of AIDS incidence.

Short-term projections of AIDS incidence are critical for assessing future health care needs. This paper focuses on the method of back-calculation for obtaining short-term projections. The approach consists of back-calculating from AIDS incidence data through use of the incubation period distribution to obtain estimates of the numbers previously infected. The numbers previously infected are then projected forward to obtain short-term projections. An approach is suggested for accounting for new infections in short-term projections of AIDS incidence. Back-calculation requires accurate AIDS incidence data. A method which is computationally easy to implement is proposed for estimating the distribution of the delays in reporting AIDS cases. It was found that the reporting delay distribution in the United States varies by geographic region of diagnosis. Back-calculation also requires a reliable estimate of the incubation period distribution. Statistical issues associated with estimating the incubation period distribution are considered. The methods are applied to obtain short-term projections of AIDS incidence in the United States. The projected cumulative AIDS incidence in the U.S. by the end of 1992 was 287,100 under the assumption that there are no new infections after 1 July 1987, and 330,600 under the assumption that the infection rate remains constant. These projections do not account for the new broadened AIDS surveillance definitions or the underreporting of AIDS cases to the Centers for Disease Control.

Acquired Immunodeficiency Syndrome

Variation in the duration of protection given by screening using the Pap test for cervical cancer.

The duration of protection offered by Pap screening for cervical cancer was examined using data on 101 cases of invasive cervical cancer and 396 controls from a Maryland case-control study. Receipt of a Pap test up to 4 years ago afforded significant protection, compared to women screened 11 or more years ago, or never screened. Smoking, intercourse before age 19, and a history of sexually transmitted disease were significant risk factors for cervical cancer; barrier contraception use was protective. Variation in protection from Pap screening was examined by age, race, age at first intercourse, barrier contraception use, and source of last Pap test (obstetrician-gynecologist vs other provider type). Results showed older women, women with earlier age of first intercourse, and non-users of barrier contraception received slightly less protection from Pap tests, while women who received their last Pap test from an obstetrician-gynecologist received significantly more protection than women who did not. Issues of quality of screening and follow-up are discussed in regard to these results.

Aged

Familial cancer history and chronic lymphocytic leukemia. A case-control study.

In a population-based case-control study carried out in the Baltimore, Maryland metropolitan area, family cancer history for 342 chronic lymphocytic leukemia cases diagnosed in 1969-1982 revealed significantly higher risks of leukemia as well as other hematolymphoproliferative neoplasms and breast cancer among their first-degree relatives compared with reported occurrence of these neoplasms in first-degree relatives of 342 matched cancer controls and 342 matched controls without cancer. Siblings of case subjects also had a significant elevation of kidney cancer compared with siblings of controls. Only one of the affected case families (and no control family) included more than one additional member with leukemia. The results suggest a genetic component for leukemia occurrence in several case families, although the majority of cases of chronic lymphocytic leukemia appeared to be sporadic. The similarity of findings between the two comparisons (cases vs. cancer controls and cases vs. controls without cancer) diminishes the likelihood of recall bias as an explanation for the observed excess risks.

Adult

Evaluation of human immunodeficiency virus seroprevalence in population surveys using pooled sera.

The pooling of individual serum samples to determine human immunodeficiency virus (HIV) seropositivity was examined to assess whether testing pooled sera was technically feasible, cost-effective, and accurate for estimating seroprevalence in large population surveys. The sensitivities and specificities of three commercially available HIV enzyme-linked immunosorbent assay (ELISA) kits were tested using 65 serum pools of 15 individual serum samples each (975 total serum samples) at two different dilutions. With pooled sera, the Organon Teknika Bio-EnzaBead ELISA at half the dilution recommended by the manufacturer showed the best agreement with ELISA and Western blot results of individual sera. In subsequently testing 92 pools, each containing 15 individual serum samples from a population of American patients attending a sexually transmitted diseases clinic, the estimated seroprevalence was 5.27 compared with 4.93% in a test of 1,380 individual serum samples and 5.19% in a test of 4,028 individual serum samples from the same population. In an evaluation of 1,380 African patients using 10 serum samples per pool, the estimated seroprevalence was 5.79 compared with 6.16% in a test of individual sera. These results indicate that ELISA testing with pooled sera is highly sensitive and specific and appears to be a cost-effective means for estimating HIV seroprevalence in large population-based surveys.

Baltimore

Modelling paired survival data with covariates.

The objective of this paper is to consider the parametric analysis of paired censored survival data when additional covariate information is available, as in the Diabetic Retinopathy Study, which assessed the effectiveness of laser photocoagulation in delaying loss of visual acuity. Our first approach is to extend the fully parametric model of Clayton (1978, Biometrika 65, 141-151) to incorporate covariate information. Our second approach is to obtain parameter estimates from an independence working model together with robust variance estimates. The approaches are compared in terms of efficiency and computational considerations. A fundamental consideration in choosing a strategy for the analysis of paired survival data is whether the correlation within a pair is a nuisance parameter or a parameter of intrinsic scientific interest. The approaches are illustrated with the Diabetic Retinopathy Study.

Actuarial Analysis

Censoring in an epidemic with an application to hemophilia-associated AIDS.

In epidemiologic studies of infectious diseases, the times of infection may be known only up to an interval. A two-stage parametric regression model is proposed for the analysis of cohort studies during an epidemic in which the exact times of infection cannot be ascertained. The methods permit joint estimation of the effects of covariates both on the risk of infection and the risk of progression to clinical disease once infected. The methodology is applied to a cohort of hemophiliacs who were at risk of infection with the AIDS virus. It was found that hemophiliacs with severe Type A hemophilia were at highest risk of infection, and the risk of infection increased sharply in the early 1980s. Hemophiliacs who were over the age of 20 at infection were at higher risk of progression to AIDS than hemophiliacs who were under age 20. The estimate of the cumulative probability of developing AIDS within t years of infection (the incubation period distribution) for hemophiliacs over age 20 was 1 - exp(-.0021t2.516). Since follow-up in this cohort was restricted to about 10 years from infection, estimates of the incubation period distribution beyond 10 years depend on model extrapolation and should be interpreted cautiously.

Acquired Immunodeficiency Syndrome

Methods for projecting course of acquired immunodeficiency syndrome epidemic.

Three methods for projecting the short-term course of the acquired immunodeficiency syndrome (AIDS) epidemic are discussed: (a) empirical extrapolation, (b) the method of "back calculation," and (c) projections based on compartmental models. Extrapolation, which requires only data on AIDS incidence, is based on an assumed functional form and on the supposition that previous trends will continue. The method of back calculation incorporates both information on previous AIDS incidence and knowledge about the incubation period distribution. These calculations provide some evidence of how many infections occurred during previous time intervals. Although this information is not precise, particularly for the recent past, it is sufficient to produce stable short-term projections. Compartmental models can be used to project future prevalence of infection as well as future AIDS incidence. However, such projections are very dependent on assumptions about initial numbers of individuals infected, rates of transmission, changes in high-risk behaviors over time, and assumptions about transmission among subpopulations with differing transmission rates and initial prevalence of infection. Thus, compartmental models offer insights into the trends in an epidemic but do not currently provide a practical tool for obtaining quantitative projections. We present projections for various risk groups based on the method of back calculation and discuss the use of additional epidemiologic data to obtain accurate projections a decade in advance.

Acquired Immunodeficiency Syndrome

Unrecognized human immunodeficiency virus infection in emergency department patients.

To determine the extent of unrecognized human immunodeficiency virus (HIV) infection, we examined blood samples drawn from patients presenting to an inner-city emergency department. We found 119 of 2302 consecutive adult patients (5.2 percent) to be seropositive for HIV. Although 27 patients presented with known symptomatic HIV infection, 92 of the remaining 2275 patients (4.0 percent) had unrecognized HIV infection. The highest seroprevalence rate (11.4 percent) was found among black men 30 to 34 years of age. Blacks, other nonwhites, and patients under the age of 45 had high rates of unrecognized infection. The clinical team established risk-factor status in only 29.0 percent of the patients. Of the 276 patients with identified risk factors, 13.0 percent were seropositive, whereas 3.1 percent of the 1616 patients with unknown risk-factor status were seropositive. None of the 102 patients who reported no risk factors were seropositive. Although penetrating trauma (seroprevalence, 13.6 percent) was the only clinical presentation associated with an increased seroprevalence rate independent of other known predictors of infection (P = 0.02), seropositive patients were found in all categories of clinical condition. These data, although based on observations in one emergency department setting, support the concept of universal blood and body-fluid precautions by all health care workers whether or not HIV infection is known.

Acquired Immunodeficiency Syndrome

Nutritional support of bone marrow transplant recipients: a prospective, randomized clinical trial comparing total parenteral nutrition to an enteral feeding program.

Although standard supportive care for bone marrow transplant (BMT) recipients includes total parenteral nutrition (TPN), it has not been shown that this is the most appropriate method of nutritional support. To determine whether current BMT recipients require TPN during the early recovery period, we conducted a prospective, randomized clinical trial comparing TPN and an individualized enteral feeding program (counseling, high protein snacks and/or tube feeding). Nutritional assessment included measurement of serum proteins, anthropometry, and body composition analysis. For the latter, total body water and extracellular fluid were measured by standard radioisotope dilution techniques and used to quantitate body cell mass and body fat plus extracellular solids (FAT + ECS). In 27 TPN patients, body composition 28 days after BMT, expressed as a percentage of baseline, was body cell mass, 100%, extracellular fluid, 108%, FAT + ECS, 108%, and in 30 enteral feeding program patients, was body cell mass, 93%, extracellular fluid, 104%, and FAT + ECS, 94%. Only the difference in FAT + ECS was statistically significant (p less than 0.01). Compared to the enteral feeding program, TPN was associated with more days of diuretic use, more frequent hyperglycemia, and more frequent catheter removal (prompted by catheter-related complications), but less frequent hypomagnesemia. There were no significant differences in the rate of hematopoietic recovery, length of hospitalization, or survival, but nutrition-related costs were 2.3 times greater in the TPN group. We conclude that TPN is not clearly superior to individualized enteral feeding and recommend that TPN be reserved for BMT patients who demonstrate intolerance to enteral feeding.

Adolescent