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Biomedical subjects

R L Prentice

Publications and source records attributed to R L Prentice.

At least 73 records · Page 4Linked to original sources

On the design of synthetic case-control studies.

A design is proposed for "case-control within cohort" studies. In this design, controls are sampled without replacement from failure-free members of the cohort at each distinct failure time. Upon selection, a subject ceases to be eligible for control selection at later failure times. Also, if a subject failing at time t had been selected as a control at t' less than t, then the matched controls at t are selected to have also been at risk at t'. In these circumstances correlation exists between score statistic contributions at t and t'. An estimator is developed for this correlation. A small simulation study compares the design just described to other possible synthetic case-control designs.

Biometry↗

Purification of two allergens from Dermatophagoides pteronyssinus using monoclonal antibodies.

Fractionation of soluble extracts from the house dust mite Dermatophagoides pteronyssinus (DP) by SDS-PAGE and crossed immunoelectrophoresis (CIE) revealed at least fifty distinct protein components. Western blotting and crossed radioimmunoelectrophoresis (CRIE) indicated that fewer than one quarter of these components were allergens as determined by their ability to bind IgE from allergic individuals. Following immunization with a crude extract, two monoclonal antibodies were raised against distinct components which exhibited IgE binding capacities in Western blot and CRIE. Affinity chromatography using these monoclonal antibodies yielded components which elicited positive skin test reactions in patients allergic to DP.

Allergens↗

Central nervous system echovirus infection in Bruton's X-linked hypogammaglobulinemia.

A patient with Bruton's X-linked hypogammaglobulinemia, who developed the typical syndrome associated with systemic echovirus 3 infection whilst on routine intramuscular gammaglobulin replacement therapy, is described. Following regular infusions of specific antibody-containing plasma from his spouse, he has shown sustained clinical improvement over a period of two years, and is, therefore, one of the very rare cases with this syndrome to survive for more than a few months.

Adolescent↗

Relative risk regression analysis of epidemiologic data.

Relative risk regression methods are described. These methods provide a unified approach to a range of data analysis problems in environmental risk assessment and in the study of disease risk factors more generally. Relative risk regression methods are most readily viewed as an outgrowth of Cox's regression and life model. They can also be viewed as a regression generalization of more classical epidemiologic procedures, such as that due to Mantel and Haenszel. In the context of an epidemiologic cohort study, relative risk regression methods extend conventional survival data methods and binary response (e.g., logistic) regression models by taking explicit account of the time to disease occurrence while allowing arbitrary baseline disease rates, general censorship, and time-varying risk factors. This latter feature is particularly relevant to many environmental risk assessment problems wherein one wishes to relate disease rates at a particular point in time to aspects of a preceding risk factor history. Relative risk regression methods also adapt readily to time-matched case-control studies and to certain less standard designs. The uses of relative risk regression methods are illustrated and the state of development of these procedures is discussed. It is argued that asymptotic partial likelihood estimation techniques are now well developed in the important special case in which the disease rates of interest have interpretations as counting process intensity functions. Estimation of relative risks processes corresponding to disease rates falling outside this class has, however, received limited attention. The general area of relative risk regression model criticism has, as yet, not been thoroughly studied, though a number of statistical groups are studying such features as tests of fit, residuals, diagnostics and graphical procedures. Most such studies have been restricted to exponential form relative risks as have simulation studies of relative risk estimation procedures with moderate numbers of disease events.

Age Factors↗

Rationale and design of cancer chemoprevention studies in Seattle.

Three cancer prevention trials are currently in their early phases at The Fred Hutchinson Cancer Research Center, the University of Washington School of Public Health and Community Medicine, and the Swedish Hospital. All 3 studies are randomized and placebo controlled. One large-scale study involves the daily administration of retinoids to persons with asbestos-related lung disease in an attempt toward reduction of their high risk for bronchogenic carcinomas and mesotheliomas. A second study involves administration of the same agents to long-term heavy smokers; a substantial feasibility and toxicity pilot study will precede a full-scale prevention trial. In the third trial, folic acid administration is evaluated in relation to the progression and regression of cervical dysplasia among women with abnormal Pap smears. We report here the rationale and the design for these 3 studies.

Asbestosis↗

Serum cholesterol, other risk factors, and cardiovascular disease in a Japanese cohort.

The relationship of serum cholesterol and other risk factors to cardiovascular disease was investigated in a 16-year cohort of 16,711 residents of Hiroshima and Nagasaki. Examined in detail were the relationship of serum cholesterol, and the joint relationships of serum cholesterol, systolic blood pressure, diastolic blood pressure, and other risk factors to coronary heart disease (CHD), cerebral infarction (CI), and cerebral hemorrhage (CH). Baseline and biennially collected risk factor data were analyzed. The latter type of measurement permitted separate investigation of both the short-term and long-term effects of cholesterol measurements. In both types of analyses, both serum cholesterol and blood pressure showed strong associations with CHD incidence. In particular, there were strong associations with short-term and delayed CHD incidence. Furthermore, the association of cholesterol with short-term CHD incidence could not be explained by its association with delayed CHD incidence, or vice versa. Multivariate analyses that also included several other risk factors (smoking habits, clinical diagnosis of diabetes mellitus, left ventricular hypertrophy or strain on electrocardiogram, relative body weight, hematocrit, and proteinuria) for which data were available showed such risk factors to be of lesser, but generally non-negligible, importance in this population. In the case of CH and CI, serum cholesterol was found to be weakly or not at all related to incidence of either disease while blood pressure remained a strong correlate. For CI some suggestion of a statistical interaction between blood pressure and serum cholesterol was found. Discussed are implications for theories of disease pathogenesis for CHD, CI and CH.

Adult↗

HLA and disease: relative-risk regression methods and multiple testing considerations.

This paper discusses certain statistical issues arising in an analysis to relate HLA-B antigens to the incidence of graft-versus-host disease in a clinical study. The Cox regression method is used to develop a global test of the hypothesis of no association and to produce estimated relative-risk factors corresponding to the presence of each particular allele. Multiple-testing considerations are central to any attempt to identify pairs of alleles having significantly different relative-risk factors. A number of simultaneous-testing approaches are considered including cumulative P-value plotting and a direct simulation of the null distribution of the maximum pairwise ratio.

Anemia, Aplastic↗

On the use of case series to identify disease risk factors.

Methods to identify disease risk factors from a series of cases are considered. These include methods that compare risk factor levels among diagnostic categories and methods that relate risk factor levels to age at diagnosis, with a single diagnostic category. Statistical aspects considered include modelling assumptions, parameter identifiability, hypothesis-testing efficiency, assumptions concerning unsampled diagnostic categories and requirements for risk factor data and confounding factor data. It is argued that methods to identify risk factors using data on a single diagnostic category involve such strong assumptions that they have limited usefulness. Analyses that compare risk factor levels among diagnostic categories, on the other hand, should continue to play an important role in epidemiologic research, though there are important limitations in relation to analyses involving disease-free controls.

Age Factors↗

Correlation of two in vitro tests with clinical response to immunosuppressive therapy in 54 patients with severe aplastic anemia.

Two in vitro tests were applied to 54 consecutive patients with severe aplastic anemia who were treated in Seattle with antithymocyte globulin. In the first test, peripheral blood mononuclear cells were collected from each patient before antithymocyte globulin therapy and then treated with a panel of monoclonal antibodies and complement. The treated peripheral blood mononuclear cells were assayed for erythroid burst-forming units (BFU-E). This test was designed to determine whether removing various subpopulations of peripheral blood mononuclear cells would increase the number of detectable BFU-E. In the second test, peripheral blood was collected within 48 hr after completion of antithymocyte globulin therapy, and cells were immediately assayed for BFU-E without any further treatment. Data from both tests were analyzed to determine whether the in vitro results correlated with patient response to therapy. Binary logistic regression analyses indicate that a modest correlation (p = 0.04) exists between test 1 in vitro results and patient response to therapy. However, the strength of this association appears to decrease as the interval between diagnosis and treatment increases. In contrast, test 2 had a very significant correlation (p = 0.001) with response to therapy among patients diagnosed more than 1 mo prior to treatment, whereas such an association was not apparent among patients treated within 1 mo of diagnosis.

Adolescent↗

The analysis of chromosomally aberrant cells based on beta-binomial distribution.

Analysis carried out here generalized on earlier studies of chromosomal aberrations in the populations of Hiroshima and Nagasaki, by allowing extrabinomial variation in aberrant cell counts corresponding to within-subject correlations in cell aberrations. Strong within-subject correlations were detected with corresponding standard errors for the average number of aberrant cells that were often substantially larger than was previously assumed. The extrabinomial variation is accommodated in the analysis in the present report, as described in the section on dose-response models, by using a beta-binomial (beta-B) variance structure. It is emphasized that we have generally satisfactory agreement between the observed and the beta-B fitted frequencies by city-dose category. The chromosomal aberration data considered here are not extensive enough to allow a precise discrimination between competing dose-response models.

Chromosome Aberrations↗

Association between HLA-B antigens and acute graft-versus-host disease.

130 patients with severe aplastic anaemia, conditioned with high-dose cyclophosphamide, showed sustained engraftment of marrow from HLA-identical siblings. Most patients (55%) had no acute graft-versus-host disease (GVHD), 11% had transient grade I, and 34% had moderate to severe (grades II-IV) acute GVHD. The relation between the donors' (and the patients') HLA antigens and the incidence of grades I-IV acute GVHD was explored. There was no association with HLA-A antigens, but a significant correlation with HLA-B antigens. Patients with HLA-B18 had an estimated acute GVHD incidence nearly three times that of other patients, whereas the incidence in the presence of HLA-B8 or HLA-Bw35 was estimated to be about half that in the absence of these alleles.

Acute Disease↗

Acquired immune deficiency syndrome. A prodromal form.

Only one case of the acquired immune deficiency syndrome (AIDS) has been conclusively documented in Australia despite a large at-risk population and the endemic nature of the syndrome in the United States. In this article, the cases of two homosexual men who had the clinical and laboratory features of a prodromal form of AIDS are presented. Such cases should serve to alert the medical profession and public health authorities to the possible existence of the syndrome in Australia.

Acquired Immunodeficiency Syndrome↗

Graft-versus-host disease and survival in patients with aplastic anemia treated by marrow grafts from HLA-identical siblings. Beneficial effect of a protective environment.

One hundred thirty patients with severe aplastic anemia were conditioned with cyclophosphamide for transplantation of marrow from HLA-identical siblings. The patients were selected for the present analysis according to the criterion of sustained marrow engraftment. Of the 130 patients, 97 are now alive between 1.4 and 11 years (median, 5) after transplantation. Twenty-nine of the thirty-three who died had either acute or chronic graft-versus-host disease (GVHD). Our analysis was directed at identifying factors predicting GVHD and survival after transplantation in patients. Our key findings were that moderately severe to severe acute GVHD had a strong adverse influence on survival; that a protective environment significantly reduced mortality, which corresponded in part to a reduction in and delayed onset of acute GVHD; that refractoriness to random-donor platelet infusions at transplantation adversely influenced survival, particularly among patients with acute GVHD; and that increasing age was associated with increased mortality.

Adult↗