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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

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Effect of HIV antibody disclosure on subsequent sexual activity in homosexual men.

During a prospective study of the natural history of AIDS, 1001 homosexual or bisexual men were offered the opportunity to learn their HIV antibody status. Six hundred and seventy (67%) of the population who elected to do so were similar to the 331 (33%) people who declined in a number of baseline characteristics. All were counselled to practice safe sex. To determine whether disclosure of HIV serologic status affects subsequent sexual behavior, we examined changes at four time-points in three sexual activities during the previous 6 months: the number of male partners with whom the participant had (1) sexual intercourse, (2) unprotected anal receptive intercourse, and (3) unprotected anal insertive intercourse. All activities decreased strikingly over the 18-month study period. Following disclosure, the mean number of partners dropped to 47% of the baseline number in people remaining unaware of their antibody status, to 45% in people told that they were seropositive, and to 55% in people told that they were seronegative. The mean number of partners for younger seropositives declined less than that for older seropositives. The mean number of partners with whom unprotected anal receptive intercourse was practiced declined to 57% of baseline in unaware people, 42% in aware seropositives, and 62% in aware seronegatives. The mean number of partners with whom unprotected anal insertive intercourse was practiced declined to 52% of baseline in unaware people, 42% in aware seropositives and 59% in aware seronegatives. Disclosure of a negative test result led to a significantly smaller decline in these sexual activities.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗

Biases in prevalent cohorts.

Several natural history studies of the Acquired Immunodeficiency Syndrome (AIDS) have been based on the follow-up of individuals infected with the AIDS virus prior to enrollment. The natural time scale for studying the preclinical course of AIDS is the time since first infection; however, in these studies the time at infection was a random unknown quantity. The biases inherent in using follow-up time instead of time from infection are investigated for estimation of both the cumulative distribution function and the hazard ratio for proportional hazards models with both fixed and time-dependent covariates. Although the magnitudes of the biases depend on the shape of the epidemic curve, a number of bounds on the biases are established. These results are useful for interpreting prevalent cohort studies and then comparing them with studies on newly infected individuals in order to assess consistency of results across studies.

Acquired Immunodeficiency Syndrome↗

Two-stage models for the analysis of cancer screening data.

Methods are proposed for the analysis of the natural history of disease from screening data when it cannot be assumed that untreated preclinical disease always progresses to clinical disease. The methodology is based on a two-stage model for preclinical disease in which stage 1 lesions may or may not progress to stage 2, but all stage 2 lesions progress to clinical disease. The focus is on joint estimation of the total preclinical duration and the sensitivity of the screening test. A partial likelihood is proposed for the analysis of prospectively collected screening data, and an analogous conditional likelihood is proposed for retrospective data. Some special cases for the joint sojourn distribution of the two stages are considered, including the independent model and limiting models where the duration of stage 2 is short relative to stage 1. The methods are applied to a case-control study of cervical cancer screening in Northeast Scotland.

Biometry↗

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↗

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↗

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↗

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↗

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↗