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Biomedical subjects

S G Baker

Publications and source records attributed to S G Baker.

At least 19 recordsLinked to original sources
PubMed1992

Graphical representation of survival curves associated with a binary non-reversible time dependent covariate.

The use of time dependent covariates has allowed for incorporation into analysis of survival data intervening events that are binary and non-reversible (for example, heart transplant, initial response to chemotherapy). We can represent this type of intervening event as a three-state stochastic process with a starting state (S), an intervening state (I), and an absorbing state (D), which usually represents death. In this paper we present three procedures for calculating survivorship functions which attempt to display the prognostic significance of the time dependent covariate. The first method compares survival from baseline for the two possible paths through the stochastic process; the second method compares overall survival to survival with state I removed from the process; and, the third method compares survival for those already in state I at a landmark time x to those in state S at time x who will never enter state I. We develop discrete hazard estimates for the survival curves associated with the three methods. Two examples illustrate how these methods can yield different results and in which situations one might employ each of the three methods. Extensions to applications with reversible binary time dependent covariates and models with both baseline and time dependent covariates are suggested.

Data Interpretation, Statistical↗
PubMed1992

Closed-form estimates for missing counts in two-way contingency tables.

One method for analyzing contingency tables with missing observations is to model the missing-data mechanism using log-linear models. Previous methods for obtaining estimates (of missing counts and parameters) have required an iterative algorithm. In many cases, however, one can obtain estimates by use of a simple algebraic formula. We illustrate the method with data on smoking and birth weight.

Algorithms↗
PubMed1991

The impact of breakthrough clinical trials on survival in population based tumor registries.

Three statistical models are developed to study the impact that two breakthrough clinical trials (MOPP for Hodgkin's disease and PVB for disseminated testicular cancer) had on survival in the Connecticut tumor registry and the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) registry program. A segmented regression model is used in conjunction with the Cox semi-parametric proportional hazards model, as well as the parametric Weibull and exponential cure models. These models allow us to determine approximately when survival first began to improve dramatically, indicating that improved treatments had become available, and how long it took for survival to level off again indicating that the full population survival impact had been realized. In addition, the degree to which the parametric models fit allows us to determine if the survival improvements occur within a parametric family. Results of the modelling indicate that dissemination took approximately 11 years in Hodgkin's disease while only 3 years in disseminated testicular cancer. In both disease sites survival first broke with prior trends between the time that the breakthrough trial started and its publication, indicating that earlier moderately successful 'precursor' trials with combination chemotherapy may have initiated the improved population survival trends. Reasons for the difference in dissemination time in the two cancer sites are examined in order to understand what factors may be responsible for the speed of dissemination and effective utilization of new therapies.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Using replicate observations in observer agreement studies with binary assessments.

By introducing replicate observations into observer agreement studies, one can obtain better measures of observer agreement than heretofore possible. New methodology based on the analysis of latent variables allows a separation of within- and between-observer variation for binary measures of assessment among pairs of observers. Maximum likelihood estimation and hypothesis testing are discussed. The methodology is illustrated using data on the assessment of dysplasia by pathologists.

Biometry↗
PubMed1990

Statistical considerations in cancer screening programs.

The goal of cancer screening is the early detection and treatment of disease, with a consequent reduction in the mortality rate. Evaluation of whether a particular screening program can achieve this goal is a difficult task. Two components of the screening process must be assessed. The first is the ability of the screening test to detect cancer early while minimizing the number of false-positive results. In this regard, the specificity of the test ordinarily must be very high, approaching 99%. No screening test for prostate cancer has yet been reported to have a specificity this high, indicating that any prostate cancer screening program using currently available tests will have to deal with the problem of a large number of false-positive findings. To evaluate the overall impact of a screening program, the best procedure is the randomized controlled trial with cancer-specific mortality as the endpoint. This endpoint is used because it avoids the lead time and length biases inherent in other outcome variables such as stage shift and case survival. The screening randomized controlled trial must be carefully planned and implemented, because it is lengthier and more costly than the usual therapy trial because of differences in study populations, trial design relative to the planned population intervention, and the extent of knowledge of disease natural history. A further important component of screening evaluation is cost. The decision to implement or continue a screening program can be aided by using cost-effectiveness analysis, which bases a decision on the ranking of cost-to-benefit ratios for the various programs contending for limited funds. Screening cost includes the cost of the test, the cost of side effects of the test, and the costs of biopsy and treatment, while screening benefit can be measured in terms of lives saved, life years saved, or quality-adjusted life years.

Cost-Benefit Analysis↗
PubMed1990

Natural history and cardiac manifestations of homozygous familial hypercholesterolaemia.

Forty-nine patients with homozygous familial hypercholesterolaemia (diagnosed on the basis of family history, xanthomatosis, total serum cholesterol and low-density lipoprotein receptor status) were studied over a period of 13 years, and underwent cardiovascular assessment. Eleven died, nine of myocardial infarction. Seven underwent coronary artery bypass, and another five had surgery to relieve supravalvular and valvular aortic stenosis. A distinctive pattern of disease was noted. Coronary ostial stenosis (four patients) and aortic root stenosis (six patients), both consequences of aortic root cholesterol deposition, were the typical manifestations of heart disease in childhood and adolescence. Adults developed severe coronary artery disease with a high incidence of main stem lesions (four of five patients). Surgery provided effective treatment for coronary artery disease and aortic outflow tract stenosis. Overall survival appeared to be better than reported in other studies which may reflect the 'receptor-defective' status of this group of patients.

Adolescent↗
PubMed1989

Prevalence of familial hypercholesterolemia in Johannesburg Jews.

The prevalence of heterozygous familial hypercholesterolemia was determined in a representative sample of 403 young Jewish men resident in Johannesburg, South Africa. Preliminary screening by measurement of serum total cholesterol demonstrated that 25 of them had levels greater than or equal to 7.5 mmol/l (290 mg/dl). On the basis of subsequent clinical, biochemical, and family studies, 6 men, or about 1 in 67 of the total sample, were considered to be heterozygotes. This very high prevalence, about 7 times greater than that found in other Caucasian populations, is probably related to founder effect. It may help to explain the high frequency of coronary heart disease in Johannesburg Jews.

Adult↗
PubMed1989

Treatment of hypercholesterolemia with the HMG CoA reductase inhibitor, simvastatin.

We report the results of a two center study on the use of the HMG Co A reductase inhibitor, simvastatin, in 44 patients suffering from familial hypercholesterolemia or from primary hypercholesterolemia of unknown etiology. The study included two separate phases: Phase I was part of a multicenter, 4-week, placebo-controlled trial; phase II was a 6-month, open extension trial, the object of which was to reduce low density lipoprotein (LDL) cholesterol levels to below the 50th percentile by increasing the dose of simvastatin, by the use of additional lipid-lowering medication, or both. Our phase I results were commensurate with those reported for the entire international cohort of 272 patients, indicating a clear dose-response relationship, with approximately 75% of the maximum reduction in LDL-C levels being achieved with 20 mg/day and over 90% of the maximum being achieved with 40 mg of simvastatin per day. In the open extension trial, the results from the 2 centers were essentially similar. Total cholesterol fell by 29% on the 20 mg/day dose and by 34% on the full dose of 40 mg/day. LDL-C levels were reduced by 40% on the 40 mg/day schedule, and triglycerides also fell to between 20% and 40% below baseline values. HDL-C concentration rose by 14% and 17.6%. The effects of simvastatin were uniform, both within and between the two cohorts. The addition of cholestyramine caused a further substantial reduction in LDL-cholesterol to below 55% of the initial value in four patients, whereas bezafibrate further enhanced the fall in triglycerides and the increase in high-density lipoprotein cholesterol, but had only a slight effect on LDL-C levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Two-process models for discrete-time serial categorical response.

This paper proposes a two-process log-linear model for analysis of polychotomous response data generated on study subjects assessed at successive discrete intervals. Response type at each discrete time may be either a transient response or a cause-specific failure. We view outcome of transient response as fundamentally different from outcome of failure, and, in a competing risk framework, we motivate a separate model for each: one to describe the process for transitions to transient response states and the other to describe the process for transitions to absorbing failure states. We maximize the likelihood for each model separately with use of existing software for iterative proportional fitting.

Aged↗
PubMed1988

Determination of cholesterol and triglycerides in blood: a comparison between wet chemistry methods and a dry chemistry analyser.

Total cholesterol and triglyceride concentrations in 127 samples of capillary and venous blood were measured with the portable Reflotron 'dry chemistry' reflectometer and compared with serum levels measured in the laboratory using wet chemistry methods. Results were grouped into low, middle and high ranges. Levels measured with the Reflotron correlated closely with those measured by wet chemistry methods. Reflotron values for both lipid fractions were, however, consistently higher than wet chemistry levels but the differences were small except at high levels. It is concluded that the Reflotron is a satisfactory instrument for providing clinically useful measurements of cholesterol and triglyceride nearer to the patient.

Cholesterol↗
PubMed1987

Prevalence of hypercholesterolaemia in young Afrikaners undergoing coronary artery bypass surgery. Ischaemic heart disease risk factors.

Ischaemic heart disease risk factors, with particular reference to familial hypercholesterolaemia, were studied in 47 male and 6 female Afrikaners, aged 55 years and under, admitted to hospital for coronary bypass surgery. The outstanding feature in this group with severe coronary atherosclerosis demonstrated angiographically was that about half had severe hypercholesterolaemia (greater than or equal to 8.5 mmol/l), and that of the severely hypercholesterolaemic patients about half again had familial hypercholesterolaemia (FH). This yielded an overall prevalence of FH in the 53 cases of 1 in 4 (26.7%) and strongly supports the contention that FH is a major risk factor for severe coronary artery disease in young Afrikaners. The only other risk factor of importance was cigarette smoking, about 80% of the patients being current or ex-smokers.

Angina, Unstable↗
PubMed1987

Prevalence of hypercholesterolaemia in young Afrikaners with myocardial infarction. Ischaemic heart disease risk factors.

Ischaemic heart disease (IHD) risk factors, with particular reference to familial hypercholesterolaemia (FH), were studied in 39 male and 12 female Afrikaners aged 55 years or under in an intensive care unit immediately after an acute myocardial infarction and in the survivors at about 3 months after the infarct. Two major risk factors were found. Firstly, about three-quarters of both male and female patients smoked more than 15 cigarettes daily. Secondly, 51% of males and 37% of females had serum cholesterol values of greater than or equal to 7.0 mmol/l and about 20% of both men and women had levels of greater than or equal to 8.5 mmol/l. Three male and 2 female patients--1:10 of the whole sample--had FH diagnosed by rigorous criteria, a prevalence similar to the figure of 1:8 predicted from the frequency of FH heterozygotes in the Afrikaans-speaking population. None of the other IHD risk factors such as hypertension, diabetes and hyperuricaemia appeared to be important. The role of obesity appeared to be indirect by virtue of its frequent association with and possible contribution to hypercholesterolaemia. Many of the patients had a history of previous IHD episodes.

Adult↗
PubMed1986

Familial hypercholesterolaemia--the need for adequate counselling and family tracing.

A search for the founder member(s) responsible for the familial hypercholesterolaemia (FH) gene(s) in the RSA inadvertently revealed the existence of a marriage which links two pedigrees in which FH occurs. This marriage could result in the birth of an FH homozygote child. The couple concerned should have--but had not--been informed of the implications of their union before their marriage. The importance of identifying individuals at risk through extensive tracing of families in which FH occurs and the relevance of subsequent counselling are illustrated.

Child↗
PubMed1986

Clonidine and the hormonal responses to graded exercise in healthy subjects.

The aim of this study was to assess the acute effects of clonidine, an alpha 2-adrenergic agonist, on hormonal responses to graded exercise in 8 healthy young men. After fasting overnight, each subject was tested on 2 mornings, 1 week apart. On one occasion he was given 200 micrograms clonidine orally and on the other identical placebo tablets, the order being randomized in a double-blind fashion over the 2 days. Thereafter each subject performed 2 successive treadmill runs, equivalent to 60 and 100%, respectively, of maximal aerobic power. Clonidine pretreatment blunted the maximal increase in plasma catecholamines by more than 60% of the control response (p less than 0.01), without significantly altering the rise of plasma cortisol or ACTH. Furthermore, clonidine significantly reduced the exercise-induced maximal rise in plasma glucose, without modifying the slight decline in mean plasma insulin or increase in pancreatic glucagon levels. The drug did not affect the maximal increments in plasma growth hormone or prolactin occurring after exercise. It was concluded that a single dose of clonidine suppressed peripheral sympathetic responses, without altering central (pituitary) alpha-adrenergic-mediated hormonal responses, to short-term exercise in healthy men.

Adrenocorticotropic Hormone↗
PubMed1986

Risk reduction for nonmelanoma skin cancer with childhood sunscreen use.

Exposure to ultraviolet radiation is the principle cause of basal and squamous cell carcinomas of the skin, which are the most frequent tumors occurring in white residents of the United States. Using a mathematical model based on epidemiologic data, we quantified the potential benefits of using a sunscreen with a sun protective factor of 15 and estimate that regular use of such a sunscreen during the first 18 years of life would reduce the lifetime incidence of these tumors by 78%. Additional benefits of sunscreen use during childhood include reduced risk of sunburn, retarding the pace of skin aging, and possible reduction in melanoma risk. We recommend that pediatricians encourage sunscreen use and sun avoidance as a regular part of pediatric preventive health care.

Adolescent↗