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Biomedical subjects

N P Jewell

Publications and source records attributed to N P Jewell.

At least 19 recordsLinked to original sources

Semiparametric estimation of proportional mean residual life model in presence of censoring.

A mean residual life function is the average remaining life of a surviving subject, as it varies with time. The proportional mean residual life model was proposed by Oakes and Dasu (1990, Biometrika77, 409-410) in regression analysis to study its association with related covariates in absence of censoring. In this article, we develop some semiparametric estimation procedures to take censoring into account. The proposed methodology is evaluated via simulation studies, and further applied to a clinical trial of chemotherapy in postoperative radiotherapy of lung cancer patients.

Antineoplastic Agents↗

Marker processes in survival analysis.

In the development of many diseases there are often associated variables which continuously measure the progress of an individual towards the final expression of the disease (failure). Such variables are stochastic processes, here called marker processes, and, at a given point in time, they may provide information about the current hazard and subsequently on the remaining time to failure. Here we consider a simple additive model for the relationship between the hazard function at time t and the history of the marker process up until time t. We develop some basic calculations based on this model. Interest is focused on statistical applications for markers related to estimation of the survival distribution of time to failure, including (i) the use of markers as surrogate responses for failure with censored data, and (ii) the use of markers as predictors of the time elapsed since onset of a survival process in prevalent individuals. Particular attention is directed to potential gains in efficiency incurred by using marker process information.

Biomarkers↗

A competing risks analysis of presenting AIDS diagnoses trends.

The proportions of gay men presenting with various AIDS diagnoses display temporal trends. In particular, the proportion of initial diagnoses reported as Kaposi's sarcoma (KS) has declined over time. Epidemiologists have hypothesized that (a) KS may require a cofactor, whose prevalence has declined over time, or (b) KS may have a shorter incubation period than other presenting diagnoses. We examine whether this latter hypothesis, considered in a competing risks framework, could account for the observed decline in KS. We nonparametrically estimate the relevant cause-specific hazard functions from the doubly-censored data of the San Francisco City Clinic Cohort by maximizing a roughness penalized likelihood using an EM algorithm. These estimates suggest that differences in the underlying cause-specific hazard functions account for a substantial portion of the observed diagnoses trends.

Acquired Immunodeficiency Syndrome↗

Generalizations of current status data with applications.

In estimation of a survival function, current status data arises when the only information available on individuals is their survival status at a single monitoring time. Here, we briefly review extensions of this form of data structure in two directions: (i) doubly censored current status data, where there is incomplete information on the origin of the failure time random variable, and (ii) current status information on more complicated stochastic processes. Simple examples of these data forms are presented for motivation.

HIV Infections↗

Estimating patterns of CD4 lymphocyte decline using data from a prevalent cohort of HIV infected individuals.

In natural history studies of chronic disease, it is of interest to understand the evolution of key variables that measure aspects of disease progression. This is particularly true for immunological variables among persons infected with the human immunodeficiency virus (HIV). The natural time scale for such studies is time since infection. Most data available for analysis, however, arise from prevalent cohorts, where the date of infection is unknown for most or all individuals. As a result, standard curve fitting algorithms are not immediately applicable. Here we propose two methods to circumvent this difficulty. The first uses repeated measurement data to provide information not only on the level of the variable of interest, but also on its rate of change, and is based on the principal curves algorithm of Hastie and Stuetzle. The second uses an external estimate of the expected time since infection. Both methods use locally-weighted linear smoothers, and are applied to data from a prevalent cohort of HIV-infected homosexual men, giving estimates of the average pattern of CD4 lymphocyte decline. These methods apply to natural history studies that use data from prevalent cohorts where the time of disease origin is uncertain, provided availability of certain information from external sources.

Algorithms↗

Different AIDS incubation periods and their impacts on reconstructing human immunodeficiency virus epidemics and projecting AIDS incidence.

The objective of this study was to investigate heterogeneity in incubation distributions in different cohorts and to assess the sensitivity of back-calculated infection rates to different assumptions about incubation times from human immunodeficiency virus (HIV) infection to AIDS diagnosis. Incubation distributions were estimated by using data from three different cohort studies. These and one other published incubation model were used as inputs for a back-calculation procedure that reconstructed smooth HIV-infection rates from AIDS incidence among adults in the United States, allowing for changes over time in incubation. Incubation estimates from the different cohorts differed substantially. The cumulative HIV incidence estimates that result from using the different incubations are very different, but the back-calculated models all produce good fits to the observed diagnosis counts. We conclude that systematic differences in incubation times of different groups add substantially to the uncertainty inherent in using the back-calculation method to reconstruct HIV epidemics and project future numbers of AIDS cases.

Acquired Immunodeficiency Syndrome↗

Statistical models for prevalent cohort data.

In prospective cohort studies individuals are sometimes recruited according to a certain cross-sectional sampling criterion. A prevalent cohort is defined as a group of individuals who have a certain disease at enrollment into the study. Statistical models for the analysis of prevalent cohort data are considered when the onset or diagnosis time of the disease is known. The incident proportional hazards model, where the time scale is duration with disease, is compared to the prevalent proportional hazards model, where the fundamental time scale is follow-up time. In certain cases the time of enrollment may coincide with another event (such as the initiation of treatment). This situation is also considered and its limitations highlighted. To illustrate the methodological ideas discussed in the paper, the analysis of data from an observational study of zidovudine (ZVD) in patients with the acquired immunodeficiency syndrome (AIDS) is presented.

Acquired Immunodeficiency Syndrome↗

An annotated bibliography of methods for analysing correlated categorical data.

This paper provides an annotated bibliography of over 100 articles concerning methods for analysing correlated categorical response data. Most of the papers listed here concern categorical regression models and estimation, with particular emphasis on binary responses. The papers are classified by several characteristics which group them according to common themes. The bibliography serves as a reference of methods for analysts of correlated categorical data, as well as for persons interested in methodologic work in this active area of statistical research.

Clinical Trials as Topic↗

Female-to-male transmission of human immunodeficiency virus.

OBJECTIVE: --To examine rates of heterosexual transmission of human immunodeficiency virus (HIV) and associated risk factors and to determine the relative efficiency of female-to-male and male-to-female transmission. DESIGN: --Survey of infected individuals and their heterosexual partners recruited since 1985. SETTING: --Participants were recruited from various HIV counseling and testing sites throughout California but were generally interviewed and tested in their homes. PARTICIPANTS: --Data from 379 couples at entry to the study are reported: 72 male partners of infected women and 307 female partners of infected men. The infected index case had a well-established source of risk; couples were eliminated if the direction of transmission could not be established. The majority of couples were monogamous since 1978, white, and in their 30s. Most partners did not know their serostatus at entry into the study. MAIN OUTCOME MEASURE: --HIV serostatus in the exposed sexual partner. RESULTS: --We observed one probable instance (1%) of female-to-male transmission compared with 20% transmission rates in the female partners of infected men. All couples were sampled in the same way. Male index cases were more likely to be symptomatic than female index cases. CONCLUSION: --The odds of male-to-female transmission were significantly greater than female-to-male transmission. The one case of female-to-male transmission was unique in that the couple reported numerous unprotected sexual contacts and noted several instances of vaginal and penile bleeding during intercourse.

Adolescent↗

CD8+ T lymphocytes and progression to AIDS in HIV-infected men: some observations.

The relationship between CD8+ lymphocyte counts and progression to AIDS was studied in 340 HIV-1-seropositive men participating in a population-based prospective study. Overall, the relative hazard for developing AIDS during 60 months of observation was slightly elevated (1.08, P = 0.003), indicating an 8% increase in risk of progression for every 100 CD8+ cell count increment. When the data were analyzed in relation to date of diagnosis, the relative hazard was depressed (0.90, P less than 0.001) for the period 6 months prior to diagnosis, but was close to 1.0 for the period 6-36 months prior to diagnosis. These findings suggest a complex relationship between CD8+ cell counts and progression to AIDS, with the possibility that various subsets of the CD8+ compartment play different roles.

Acquired Immunodeficiency Syndrome↗

Nonparametric estimation of the incubation period of AIDS based on a prevalent cohort with unknown infection times.

Estimation of the incubation period distribution of human immunodeficiency virus based on prevalent cohorts of subjects, already infected at the time of recruitment, is complicated by the absence of information on the original times of infection. Here, we overcome this difficulty by using a prior distribution for the infection times, based on external data. Our estimate is nonparametric, but uses smoothness assumptions to avoid instability. The method is illustrated on two prevalent cohorts from San Francisco, separately and combined. The estimates produced agree with other published estimates of the incubation period distribution.

Acquired Immunodeficiency Syndrome↗

Some statistical issues in studies of the epidemiology of AIDS.

Analysis of studies of the epidemiology and natural history of infection with the Human Immunodeficiency Virus and subsequent onset of AIDS are complicated by many statistical issues. Several such problems are associated with the nature of data collection which is often incomplete. Here we briefly survey some of the statistical methods that have been developed to meet the needs of analysis of AIDS data. In particular, we consider projection of the number of future cases, and estimation and identification of two key epidemiological unknowns, namely the properties of the incubation distribution and those of the infectivity associated with transmission.

Acquired Immunodeficiency Syndrome↗

The effect of number of exposures on the risk of heterosexual HIV transmission.

Several studies of the heterosexual transmission of human immunodeficiency virus have reported no association between transmission and number of exposures. In contrast, this study showed that for a susceptible sex partner, the number of exposures to an infected index case is indeed associated with transmission, but in a nonlinear fashion. Factors that can dilute an association between transmission and number of exposures include measurement error in calculating number of exposures, use of inappropriate statistical models, and failure to account for variations in transmission rates. For example, the practice of anal intercourse and the experience of bleeding during intercourse increase the likelihood of transmission. We also observed that transmission occurred with fewer exposures among couples who did not use condoms compared with couples who did. The number of exposures also affects the independent association between other risk factors and transmission and thus should be considered when analyzing other sources of risk.

Adolescent↗

Statistical analysis of HIV infectivity based on partner studies.

Partner studies produce data on the infection status of partners of individuals known or assumed to be infected with the human immunodeficiency virus (HIV) after a known or estimated number of contacts. Previous studies have assumed a constant probability of transmission (infectivity) of the virus at each contact. Recently, interest has focused on the possibility of heterogeneity of infectivity across partnerships. This paper develops parametric and nonparametric procedures based on partner data in order to examine the risk of infection after a given number of contacts. Graphical methods and inference techniques are presented that allow the investigator to evaluate the constant infectivity model and consider the impact of heterogeneity of infectivity, error in measurement of the number of contacts, and regression effects of other covariates. The majority of the methods can be computationally implemented easily with use of software to fit generalized linear models. The concepts and techniques are closely related to ideas from discrete survival analysis. A data set on heterosexual transmission is used to illustrate the methods.

Biometry↗

The effect of retrospective sampling on binary regression models for clustered data.

Recently a great deal of attention has been given to binary regression models for clustered or correlated observations. The data of interest are of the form of a binary dependent or response variable, together with independent variables X1,...., Xk, where sets of observations are grouped together into clusters. A number of models and methods of analysis have been suggested to study such data. Many of these are extensions in some way of the familiar logistic regression model for binary data that are not grouped (i.e., each cluster is of size 1). In general, the analyses of these clustered data models proceed by assuming that the observed clusters are a simple random sample of clusters selected from a population of clusters. In this paper, we consider the application of these procedures to the case where the clusters are selected randomly in a manner that depends on the pattern of responses in the cluster. For example, we show that ignoring the retrospective nature of the sample design, by fitting standard logistic regression models for clustered binary data, may result in misleading estimates of the effects of covariates and the precision of estimated regression coefficients.

Cluster Analysis↗

Colonoscopic screening of persons with suspected risk factors for colon cancer: II. Past history of colorectal neoplasms.

Colonoscopic screening has been recommended for all persons who have had a colorectal adenoma or carcinoma. Such persons have been assumed to be at increased risk of having additional, asymptomatic colorectal neoplasms, the removal of which would reduce morbidity and mortality from colorectal cancer. In this prospective study, initial colonoscopy was performed on 544 asymptomatic subjects with past histories of colorectal index lesions ranging from small tubular adenomas to invasive cancers. In 402 subjects whose worst index lesion was an adenoma, the prevalence of neoplasms detected at colonoscopy, above the reach of the rigid sigmoidoscope, increased with age, male sex, black race, and the number and size of their index adenomas. In 142 subjects whose worst index lesion was invasive cancer, colonoscopy findings were marginally related to age and white race. A subgroup of 133 subjects whose worst index lesion was a single, small (less than 10 mm) tubular adenoma and who had no first-degree relatives with colorectal cancer had only a 3% prevalence of advanced colonic neoplasms (tubular adenomas greater than or equal to 10 mm in diameter; tubulovillous, villous, or severely dysplastic adenomas; or invasive cancers) found on colonoscopy--no greater than would be expected in the general population. Subgroups of the remaining 411 subjects, who had advanced or multiple index lesions, had prevalences of advanced neoplasms ranging from 8% to 18%. These findings indicate that for persons whose only risk factor is a single small tubular adenoma, current screening guidelines could be modified to recommend techniques less costly and less invasive than colonoscopy.

Adenoma↗