Biomedical subjects

R Brookmeyer

Publications and source records attributed to R Brookmeyer.

87 records · Page 5Linked to original sources

PubMed1986

Minimum size of the acquired immunodeficiency syndrome (AIDS) epidemic in the United States.

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.

Acquired Immunodeficiency Syndrome↗

PubMed1986

Serum beta-carotene, vitamins A and E, selenium, and the risk of lung cancer.

We studied the relation of serum vitamin A (retinol), beta-carotene, vitamin E, and selenium to the risk of lung cancer, using serum that had been collected during a large blood-collection study performed in Washington County, Maryland, in 1974. Levels of the nutrients in serum samples from 99 persons who were subsequently found to have lung cancer (in 1975 to 1983) were compared with levels in 196 controls who were matched for age, sex, race, month of blood donation, and smoking history. A strong inverse association between serum beta-carotene and the risk of squamous-cell carcinoma of the lung was observed (relative odds, 4.30; 95 percent confidence limits, 1.38 and 13.41). Mean (+/- SD) levels of vitamin E were lower among the cases than the controls (10.5 +/- 3.2 vs. 11.9 +/- 4.90 mg per liter), when all histologic types of cancer were considered together. In addition, a linear trend in risk was found (P = 0.04), so that persons with serum levels of vitamin E in the lowest quintile had a 2.5 times higher risk of lung cancer than persons with levels in the highest quintile. These data support an association between low levels of serum vitamin E and the risk of any type of lung cancer and between low levels of serum beta-carotene and the risk of squamous-cell carcinoma of the lung.

Aged↗

PubMed1986

Matched case-control designs and overmatched analyses.

In a 1:1 matched-pairs case-control study, several pairs may have the same matching criteria. The objective of this paper is to consider various analytic approaches for odds ratio estimation in this situation. One approach is to perform the usual matched-pairs analysis; the alternative is to combine pairs into strata and compute the conditional maximum likelihood or Mantel-Haenszel estimate. Matched-pairs analysis based on theoretic and simulation results may give misleading inferences, although on average it performs nearly as well as the stratified analysis. The occasional poor performance of the matched-pairs analysis results from the possibility of obtaining an extreme number of discordant pairs due to the random pairing within a stratum. It is concluded that the prudent policy is to perform a stratified rather than a paired analysis, even at the expense of additional computation.

Epidemiologic Methods↗

PubMed1986

Covariate-dependent genetic counseling in Huntington's disease.

From detailed study of a population-based sample of active cases of Huntington's disease it is known that the age of onset of Huntington's disease is strongly affected by whether Huntington's disease was inherited from mother or father. Standard methods for genetic counseling risk computations use age of unaffected consultant as a covariate affecting the quoted risk, but no other covariates are used in these risk computations. We demonstrate the feasibility of using a proportional hazards approach to computation of the penetrance function which in turn enables a risk to be computed incorporating other covariates besides age of consultant. When there is only one significant covariate other than age, direct estimation of age-of-onset distributions corresponding to various values of the covariate also gives useful results. Our analyses show that genetic counseling risks based on covariates are feasible to compute and offer additional accuracy to the recipient of the information.

Adult↗

PubMed1986

Chronic lymphocytic leukemia and acquired disorders affecting the immune system: a case-control study.

The relationship of a number of subacute or chronic infectious diseases, connective tissue or autoimmune disorders, allergic conditions, and surgical excision of lymphoid tissue with chronic lymphocytic leukemia (CLL) was examined in a case-control study involving 342 cases and 342 matched controls. In both analyses of all matched pairs and those pairs in which both subjects were respondents, no statistically significant association was found between a history of subacute viral infections or subacute and chronic bacterial infections and CLL. Connective tissue or autoimmune disorders also were found not to be associated with CLL. Examination of the association between several allergic conditions and CLL suggested a protective effect as did a "dose-response" analysis, although none of the individual disorders showed a statistically significant relationship; however, a test for linear trend was significant (P = .04). Similarly, examination of the relationship between surgical excision of lymphoid tissue in several anatomic locations and CLL showed a protective effect, statistically significant for tonsillectomy-adenoidectomy (odds ratio = 0.69; 95% confidence interval = 0.48, 0.98). A statistically significant negative dose-response relationship, substantiating the protectiveness of the effect, was found.

Aged↗

PubMed1985

Assessing the impact of additional follow-up in cohort studies.

An approach is described for predicting the statistical value of extending follow-up in a cohort study. A simple approximation to the expected number of new events of interest is given. The effect of these events on inferences for parameters such as a standardized mortality ratio is approached in two ways. The first concerns the probability of reversing the conclusion of a significance test. The second approach finds the plausible range of values for the standardized mortality ratio after further follow-up that are consistent with the currently available data. Each of these values is displayed together with the precision of the estimate. The methods are illustrated with results from the International Radiation Study of Cervical Cancer (IARC Scientific Publication No. 52, 1984).

Biometry↗

PubMed1985

Autologous bone marrow transplantation in acute leukemia: a phase I study of in vitro treatment of marrow with 4-hydroperoxycyclophosphamide to purge tumor cells.

This phase I study was conducted to determine the maximal safe concentration of 4-hydroperoxycyclophosphamide (4HC) that could be used for in vitro treatment of bone marrow from patients with acute leukemia undergoing autologous bone marrow transplantation. Concentrations of 40 to 120 micrograms/mL of 4HC were used in 30 patients with relapsed or high-risk acute leukemia and in six patients with nonleukemic malignancies. All patients received marrow-lethal cytoreductive therapy followed by infusion of the 4HC-treated marrow. Complete inhibition of granulocyte and macrophage colony-forming cells was obtained at 80 micrograms/mL. Nevertheless, only one transplant-related death and otherwise full hematologic recovery was observed at concentrations of 4HC up to 100 micrograms/mL. At 120 micrograms/mL, there were three transplant-related deaths, including two of the three patients who required the infusion of reserve marrow. Among the acute leukemia patients, three remain in complete remission at 1,337, 1,017, and 967 days after transplant. Among the nonleukemic patients, two remain in complete remission at 1,081 and 1,017 days after transplant. At the maximum safe concentration of 4HC (100 micrograms/mL), satisfactory hematologic recovery can be obtained, despite elimination of detectable hematopoietic progenitors.

Acute Disease↗

PubMed1985

The effect of additional follow-up and accrual on survival time data.

A method called partial completion is proposed for predicting the gain in precision of the Kaplan-Meier survival curve associated with additional follow-up and accrual. This is accomplished by using the initial data to predict the numbers of patients who would be at risk at the observed death times by the end of the proposed second follow-up period. A consistency result ensures that the predictors will be accurate in large samples while simulation results suggest that the predictors are accurate with moderate sample sizes. The procedures are applied to a bone marrow transplant study and the Channing House data set.

Biometry↗

PubMed1983

Marrow transplantation for acute nonlymphocytic leukemia after treatment with busulfan and cyclophosphamide.

Fifty-one patients with acute nonlymphocytic leukemia (16 with end-stage disease, 17 in second or third remission or in early relapse, and 18 in first remission) were given infusions of HLA-identical sibling marrow after cytoreduction with high doses of busulfan and cyclophosphamide. Actuarial two-year survival rates were 0 per cent, 29 per cent, and 44 per cent, respectively. Twelve patients are still alive and in remission after 327 to 1488 days, with 10 surviving beyond two years. Acute graft-versus-host disease and viral pneumonia were the major causes of death. Leukemic cells failed to clear in one patient with end-stage disease, and a relapse with meningeal leukemia occurred in another. Only one other relapse was seen--in a patient given a transplant during a third remission. Survival was favorably affected by younger age and transplantation during first remission. We conclude that high-dose chemotherapy with busulfan and cyclophosphamide, followed by allogeneic-marrow transplantation, can produce long-term remission of acute leukemia. Chemotherapy with high-dose busulfan and cyclophosphamide before transplantation provides an effective alternative to cyclophosphamide and total-body irradiation before transplantation for the treatment of acute nonlymphocytic leukemia.

Acute Disease↗

PubMed1983

The diversity of T cell receptors specific for self MHC gene products.

Cytolytic and helper T cells exhibit, in addition to their specificity for foreign antigen, a restriction specificity for self MHC gene products. The present study was designed to assess the degree of diversity within the repertoire of receptors that are involved in T cell recognition of self MHC gene products. For this purpose, we generated a series of murine cytolytic T lymphocyte (CTL) clones specific for a hapten antigen and restricted to the self MHC gene product H-2Kb. An analysis of the hapten fine specificity of these clones by using hapten analogues revealed the presence of substantial diversity within the repertoire of CTL receptors specific for the hapten. The degree of diversity within the repertoire of self H-2 recognition structures on these clones was assessed by testing clones on panels of syngeneic, congenic H-2K disparate, and H-2Kb mutant target cells bearing varying amounts of antigen. A striking degree of heterogeneity in H-2K recognition was found among these H-2Kb restricted CTL. We estimate that there are probably a minimum of 65 different patterns of H-2K recognition among these clones. Our results suggest a high degree of diversity exists within the repertoire of self MHC recognition structures on antigen-specific T cells restricted to a single self MHC gene product.

Animals↗

PubMedDate not supplied

Methods for projecting the incidence and prevalence of chronic diseases in aging populations: application to Alzheimer's disease.

Projections of the incidence and prevalence of disease are important for public health planning. This paper describes methods for projecting the incidence and prevalence of a chronic disease in ageing populations. The approach uses age-specific disease incidence rates together with assumptions about survival to reconstruct disease prevalence. The methods can be used to evaluate the potential impact of public health interventions that may prevent disease or prolong survival. We used the methods to project the future prevalence of Alzheimer's disease in the United States. We found that the prevalence of Alzheimer's disease will nearly quadruple over the next 50 years. Although projections of the absolute prevalence are sensitive to assumptions about the age-specific incidence rates of disease, the proportionate growth is relatively insensitive. The increase in prevalence results from the ageing of the U.S. population. In order to perform the calculations, we have assembled U.S. Census population projections and U.S. mortality rates into computer software that is available from the authors at www.jhsph.edu/Departments/Biostats/software.h tml.

Aged↗

PubMedDate not supplied

Prediction intervals for survival data.

This paper concerns large sample prediction intervals for the survival times of a future sample based on an initial sample of censored survival data. Simple procedures are developed for obtaining non-parametric and exponential prediction intervals for the future sample quantiles; the non-parametric interval results from inversion of an appropriate test statistic. A simulation study performed under various conditions evaluates the accuracy of the proposed intervals. An adjuvant chemotherapy study of breast cancer patients illustrates the methodology.

Breast Neoplasms↗

PubMedDate not supplied

An application of Bayesian analysis to medical follow-up data.

Posterior distributions can provide effective summaries of the main conclusions of medical follow-up studies. In this article, we use Bayesian methods for the analysis of survival data. We describe posterior distributions for various parameters of clinical interest in the presence of arbitrary right censorship. Non-informative reference priors result from transformation of a two-parameter Weibull model into a location-scale family. We suggest an approach for checking adequacy. For illustration, we apply the methods to a well-known acute leukemia data set.

Bayes Theorem↗

PubMedDate not supplied

Case-control studies for estimation of the natural history of preclinical disease from screening data.

The duration of the detectable preclinical phase of disease, which we call the sojourn time, is an important quantity to consider when recommending frequency of screens and investigating the natural history of the disease. In this paper, we propose a matched case-control methodology for screening data for joint estimation of the sojourn time distribution and the false negative rate of the screening test. The approach is based on a conditional likelihood for matched sets that involves a comparison of the screening histories of cases and controls. We illustrate the methodology with the data from the Aberdeen screening programme for cervical cancer by the Pap smear. We consider a number of different parametric forms for the sojourn time distribution.

Biometry↗

PubMedDate not supplied

Energy requirements of parenterally fed bone marrow transplant recipients.

To determine the energy intake (kcal/kg/day) necessary to maintain zero nitrogen balance (assuming adequate protein intake) during the first 30 days after transplant, we studied 91 bone marrow transplant recipients. Serial nitrogen balance and concomitant energy and protein intakes were determined prospectively on each patient. Eight-four (92%) of the patients (ages 4-49 yr) had sufficient data for evaluation. For each patient, a simple linear model (nitrogen balance vs energy intake) was used to determine the patient's predicted individual energy requirement during the first 30 posttransplant days (EReq30). Weighted least squares multiple regression was used to determine the effect on EReq30 of such variables as age and sex. Energy requirements were significantly (p less than 0.001) greater for children, males, and patients with acute graft-vs-host disease, and when the percent of the total energy intake given by the intravenous route was high. An equation that incorporated these variables was developed to predict the energy requirements for bone marrow transplant recipients during their first 30 posttransplant days. Although individual energy requirements vary, this equation is a useful guide for initial energy prescriptions.

Adolescent↗