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Biomedical subjects

R Brookmeyer

Publications and source records attributed to R Brookmeyer.

At least 73 records · Page 4Linked to original sources
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1987

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↗
PubMed1987

Predictors of the acquired immunodeficiency syndrome developing in a cohort of seropositive homosexual men.

In a cohort of 1835 homosexual men who were seropositive for human immunodeficiency virus (HIV) on entry into a prospective study, the acquired immunodeficiency syndrome (AIDS) developed in 59 during a median follow-up of 15 months. We matched 5 seropositive controls to each case according to study center and date of enrollment and performed a case-control analysis to determine factors predictive of AIDS. In a multivariate analysis, a decreased number of T helper lymphocytes, an increased number of T suppressor lymphocytes, a low level of antibody to HIV, a high titer of cytomegalovirus antibody, and a history of sex with someone in whom AIDS developed were independently associated with subsequent AIDS. Separate analyses of risk factors for Kaposi's sarcoma and opportunistic infections failed to support previously reported associations between the use of nitrites or an elevated cytomegalovirus-antibody titer and Kaposi's sarcoma. These variables may be markers rather than determinants of disease progression. A vigorous antibody response to HIV infection may confer at least temporary protection against the progression of immunodeficiency to AIDS, or a low level of antibody to HIV may reflect a later stage of infection. The increased risk associated with a history of sex with someone in whom AIDS developed may indicate earlier infection in cases or infection with a more virulent strain of HIV. These results may be useful in counseling HIV-seropositive persons and in designing studies of clinical interventions.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Factors influencing the age at natural menopause.

To examine sociodemographic, menstrual, reproductive, and other factors which may influence the age at natural menopause, the authors analyzed data from a large series of women participating in a nationwide breast cancer screening program conducted between 1973 and 1980. Standard life table techniques permitted assessment of factors suspected of varying the time to menstrual cessation among 983 premenopausal women, 1091 surgically menopausal women, and 1423 naturally menopausal women. The median age at natural menopause was 51.1 years. Multivariate analysis indicated that parity, irregularity of menstrual cycles before age 25 or first livebirth, and high socioeconomic status were significantly related to menopausal age. These data provide evidence for the hypothesis that certain environmental and hormonal factors which affect ovulation during reproductive years may ultimately postpone the menopause.

Adult↗
PubMed1987

Delayed hypersensitivity skin testing and anergy in a population of gay men.

Anergy is almost universal among patients with the acquired immunodeficiency syndrome (AIDS). To determine the prevalence and correlates of anergy in a population at risk for AIDS, we performed skin tests in 1120 gay men who were enrolled in a prospective study of the natural history of human immunodeficiency virus (HIV) infection. Anergy, defined as no induration to any of four intradermal antigens, was present in 12%. Individually, no induration was detected in response to tetanus toxoid (41%), mumps (28%), candida (47%), and trichophyton (72%). Anergy was strongly associated with the presence of antibody to HIV and with a reduced number of T helper lymphocytes, but not independently with generalized lymphadenopathy, the number of reported male sexual partners in the previous 2 years, the number of T suppressor lymphocytes, or with high titers of antibodies to cytomegalovirus. Nine percent of HIV antibody-negative subjects and 20% of antibody-positive subjects were anergic; anergy is not specific for serologically documented HIV infection in this population. Skin testing with only tetanus toxoid, candida, and mumps antigens may be sufficient to detect anergy. In the presence of HIV antibody, the ability of anergy to predict progressive immunodeficiency remains to be determined.

AIDS-Related Complex↗
PubMed1987

The prevalent cohort study and the acquired immunodeficiency syndrome.

The acquired immunodeficiency syndrome (AIDS) is caused by a retrovirus, the human immunodeficiency virus (HIV). A rapid and convenient method to identify additional cofactors or risk modifiers and markers of disease progression is to study a cohort prevalent with HIV antibody. However, because the time of viral infection is usually unknown in the cohort, there are several potential sources of bias. Three sources of bias in a prevalent cohort study are identified assuming a proportional hazards model: onset confounding, differential length-biased sampling, and frailty selection. A number of problems in the interpretation of results on markers from a prevalent cohort also are considered. It is concluded that risk estimates derived from a prevalent cohort are not directly comparable to risk estimates derived from an incident cohort.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Factors associated with prevalent human immunodeficiency virus (HIV) infection in the Multicenter AIDS Cohort Study.

Interviews regarding medical history, life-style, specific drug taking and sexual activities, and physical examinations were administered to 4,955 homosexual men who volunteered for the Multicenter AIDS Cohort Study in Baltimore, Chicago, Los Angeles, and Pittsburgh. Overall, the prevalence of antibodies to human immunodeficiency virus (HIV) in these men was 38.0%. The factor most strongly associated with prevalent HIV infection according to a multiple logistic regression model was rectal trauma, a composite variable which included receptive anal fisting, enemas before sex, reporting of blood around the rectum, and the observation of scarring, fissures or fistulas on rectal examination. Receptive anal intercourse also was strongly associated with HIV infection in the model. The multivariate relative odds for HIV antibody positivity was 7.72 for the highest level of rectal trauma and 3.04 for receptive anal intercourse. Symptoms reported to occur in some persons who subsequently develop acquired immunodeficiency syndrome (AIDS) were frequent among HIV seropositive men (12.9%) but were reported in 8.4% of seronegative men as well. Generalized lymphadenopathy was observed significantly more often in seropositive men (48.8%) compared with seronegative men (11.4%). The prevalence of HIV antibodies was inversely related to the number of T-helper cells and directly related (to a lesser extent) to the number of T-suppressor cells. The results suggest that disruption of the rectal mucosa provides access by HIV to the blood stream and to specific immunologic cells. Since symptoms and generalized lymphadenopathy were often reported among seronegative men, they probably also occur among some seropositive men not currently progressing to AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Serologic precursors of cancer. I. Prediagnostic serum nutrients and colon cancer risk.

A study was undertaken to determine whether prediagnostic serum levels of retinol, beta-carotene, vitamin E, and selenium are lower in colon cancer cases compared with matched, population-based controls. Sera were available from 25,802 participants of a serum collection campaign conducted in Washington County, Maryland in 1974. The authors identified from these participants 72 white colon cancer cases, who were first diagnosed with colon cancer during 1975-1983, and 143 white, living, cancer-free controls, matched to cases on the basis of age, sex, month of serum collection, and enumeration in a 1975 private census of Washington County. The mean values of serum nutrients in cases and controls, respectively, were 59.1 micrograms/dl and 61.8 micrograms/dl for retinol (p = 0.22), 32.9 micrograms/dl and 34.4 micrograms/dl for beta carotene (p = 0.52), 1.17 mg/dl and 1.27 mg/dl for vitamin E (p = 0.10), and 11.0 micrograms/dl and 11.5 micrograms/dl for selenium (p = 0.07). There were no consistent trends in the relative odds of colon cancer by quintiles of serum levels for any of the nutrients; however, a relative odds of 3.2 (95% confidence interval = 1.1-8.7) was found when persons in the four lowest quintiles of retinol were compared with those in the highest. No interactions with matching factors or between serum nutrients and no confounding effects of covariables were identified through conditional logistic regression analysis. The findings of this study do not support a strong association of low serum levels of retinol, beta-carotene, vitamin E, and selenium with an increased risk of subsequent colon cancer.

Adult↗