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Biomedical subjects

J Whitehead

Publications and source records attributed to J Whitehead.

At least 19 recordsLinked to original sources
PubMed1992

Overrunning and underrunning in sequential clinical trials.

In a sequential (or group sequential) clinical trial the fulfillment of some pre-specified stopping rule will cause recruitment to be terminated. However, for various reasons, data on patients treated according to protocol may continue to accumulate for some time afterward. This phenomenon is called overrunning. On the other hand, a sequential clinical trial might be abandoned before the stopping rule has been fulfilled. This is called underrunning. In both of these situations the procedure for validly analyzing the study is unclear. In this paper we first review the arguments for sequential methodology and the practical way in which it can be integrated with normal clinical trial conduct. Turning next to the special situations of overrunning and underrunning, the conditions under which a valid analysis is possible are identified, and a method of analysis based on the frequentist philosophy is presented. The likelihood of first gaining and then losing significance due to overrunning and its consequences are examined. Examples based on experience with real studies are presented.

Clinical Trials as Topic↗
PubMed1992

Riboflavin deficiency and iron absorption in adult Gambian men.

Iron absorption from 3.38 mg 58Fe was measured in riboflavin-deficient Gambian men with haemoglobin (Hb) less than 11.5 g/dl before and after oral riboflavin therapy, and the results compared with a group not receiving riboflavin. Riboflavin status (as determined by erythrocyte glutathione reductase activation coefficient) and Hb increased in teh riboflavin-supplemented but not placebo group. Plasma ferritin levels were low and did not change in either group. There was very wide variation in percentage iron absorption between individuals and also within single individuals on two separate occasions but no measurable change with riboflavin supplementation. The results of the study indicate that the efficiency of iron utilization is impaired in riboflavin deficiency, but that iron absorption is unaffected.

Administration, Oral↗
PubMed1992

Estimating the ventilation-perfusion distribution: an ill-posed integral equation problem.

The distribution of ventilation-perfusion ratio over the lung is a useful indicator of the efficiency of lung function. Information about this distribution can be obtained by observing the retention in blood of inert gases passed through the lung. These retentions are related to the ventilation-perfusion distribution through an ill-posed integral equation. An unusual feature of this problem of estimating the ventilation-perfusion distribution is the small amount of data available; typically there are just six data points, as only six gases are used in the experiment. A nonparametric smoothing method is compared to a simpler method that models the distribution as a histogram with five classes. Results from the smoothing method are found to be very unstable. In contrast, the simpler method gives stable solutions with parameters that are physiologically meaningful. It is concluded that while such smoothing methods may be useful for solving some ill-posed integral equation problems, the simpler method is preferable when data are scarce.

Animals↗
PubMed1991

A random effects model for ordinal responses from a crossover trial.

Crossover studies have been successfully conducted in the case of continuous responses. Existing procedures of analysis for ordinal responses, on the other hand, are rarely satisfactory unless strict, usually unrealistic, assumptions are made. In this paper we investigate a random effects model and show that the model is simple and general. Interpretation of parameters is easy, though with a complicated fitting procedure.

Clinical Trials as Topic↗
PubMed1991

A general parametric approach to the meta-analysis of randomized clinical trials.

Meta-analysis provides a systematic and quantitative approach to the summary of results from randomized studies. Whilst many authors have published actual meta-analyses concerning specific therapeutic questions, less has been published about comprehensive methodology. This article presents a general parametric approach, which utilizes efficient score statistics and Fisher's information, and relates this to different methods suggested by previous authors. Normally distributed, binary, ordinal and survival data are considered. Both the fixed effects and random effects model for treatments are described.

Humans↗
PubMed1991

Analysis of failure time data with ordinal categories of response.

When failure times are observed, additional information concerning the type of failure is often recorded. A method which simultaneously models the failure times and additional information in the form of ordinal categories is discussed. An application to clinical trial data, in which the failure times are times of onset of headache, and the headaches are classified into the ordinal categories mild, moderate and severe, illustrates how this method may be used and how the final model can be interpreted. The continuation ratio model, which is used in this method, is described in detail.

Clinical Trials as Topic↗
PubMed1991

An investigation into the effect of different intakes of vitamin C on drug metabolism in Gambian men.

Hepatic mixed-function oxidase activity was measured in Gambian men during a period of low seasonal vitamin C intake and after vitamin C supplementation. Demethylation of methoxyphenylacetamide (methacetin) was followed using a breath test, in which the exhalation of 13C-enriched CO2 was measured following an oral dose of 13C-methacetin. Vitamin C supplementation, sufficient to increase plasma levels significantly, did not influence methacetin metabolism. However, methacetin metabolism in unsupplemented men appeared normal in the majority of cases. Hepatic tissue may not have been sufficiently depleted of vitamin C to impair the activity of the mixed function oxidase system.

Acetamides↗
PubMed1990

An improved approximation for calculation of confidence intervals after a sequential clinical trial.

A method for the calculation of confidence intervals following a sequential clinical trial is proposed which is more accurate than methods based solely on continuous monitoring assumptions, but is not as computationally laborious as previous methods suggested for group sequential trials. The calculation takes account of the excess of the sample path over the boundary at the final inspection of the trial, which may be substantial after group sequential monitoring, and is ignored when continuous monitoring is assumed. Accuracy of such confidence intervals after a triangular test is investigated by simulation of coverage probabilities, individual confidence limit probabilities and p-value curves.

Clinical Trials as Topic↗
PubMed1989

Comparison of the information in two lung function experiments.

The amount of ventilation relative to perfusion (the ventilation-perfusion ratio) received by the lung is a useful indicator of the efficiency of lung function. Two alternative techniques for recovering the ventilation-perfusion ratio are outlined. While both techniques rely on the use of inert gases, one is well established and the other is only in a developmental stage. This paper focuses on a comparison of the amount of statistical information provided by these two techniques about the ventilation-perfusion ratio. The criterion applied here for measuring amount of information has roots in communication theory and uses ideas inherent to Bayesian inference.

Bayes Theorem↗
PubMed1989

The analysis of relapse clinical trials, with application to a comparison of two ulcer treatments.

Patients cured of ulcers, carcinomas or other recurrent conditions are randomized between two treatments designed to maintain their recovery. Spontaneous reporting of relapse is supplemented by periodic asymptomatic screening. Interest centres on the difference in times to relapse between the two treatments. However, the analysis is complicated by the times to diagnoses at screens being qualitatively different from the times to symptomatic diagnoses between screens. In this paper a number of approaches to the analysis of such data are explored, and one of them is recommended. An extensive example with data on ulcer recurrence is presented to illustrate the method.

Adult↗
PubMed1989

Fungal contamination of mini peak flow meters.

Sixteen peak expiratory flow meters from the Outpatient Department of Solihull Hospital were dismantled for inspection and washing. Fungal contamination was found in all 16 machines with visible contamination in four.

Equipment Contamination↗
PubMed1989

Risk factors for breast cancer by mode of diagnosis: some results from a breast cancer screening study.

We have investigated factors affecting the probability that a woman with breast cancer participating in a mammographic screening programme will be diagnosed by the screen. Data from a large American case-control study, with subjects drawn from women participating in an annual screening programme, were used. During the screening programme, 409 cases were identified, the mode of diagnosis being screen detection for 331 and interval detection for 78. No significant relationships were found between mode of diagnosis and age, age at menarche, oral contraceptive use, age at first live birth, age at menopause or history of maternal breast cancer. There was a non-significant trend for particular mammographic patterns to be associated with interval detection. However relative risk of breast cancer and probability of interval detection were observed to increase about the time of the menopause. These results suggest that the 3 yearly mammography programme being introduced in the UK might be improved if an extra examination was included around the time of the menopause.

Breast Neoplasms↗
PubMed1988

Systemic mycotic disease of captive crocodile hatchling (Crocodylus porosus) caused by Paecilomyces lilacinus.

The sudden death occurred of a captive Estuarine crocodile hatchling (Crocodylus porosus). On autopsy, granuloma-like lesions were seen in the liver, left lung and spleen, and branching, septate fungal hyphae were observed in sections of liver and spleen. The fungus isolated from the liver showed characteristics of both Paecilomyces lilacinus and Paecilomyces marquandii but was closer to the former species. This is apparently the first report of the isolation of this fungus from a reptile in Australia.

Alligators and Crocodiles↗
PubMed1986

Diffusion-related differences in elimination of inert gases from the lung.

Partial pressures of intravenously infused acetylene, Freon 22, and isoflurane (gases with similar solubilities in blood but differing molecular weights) were compared in arterial and mixed venous blood and mixed expired gas of 13 anesthetized mongrel dogs to determine whether gas molecular weight influenced gas exchange. Analysis of covariance was used to account for the variables of ventilation-perfusion ratio, partition coefficient, and experimental run before individual gas effects were sought. A gas effect difference was observed such that the arterial fractional retention of isoflurane (mol wt 184.5) would be 12% higher than that of acetylene (mol wt 26) if the two gases had identical partition coefficients. This effect was neither significantly increased by positive end-expiratory pressure nor decreased by high-frequency oscillatory ventilation. To test whether the individual gas effect was greater with gases with disparate erythrocyte and plasma partition coefficients, the exchange of ethyl iodide (erythrocyte-to-plasma solubility ratio 8.1) and diethyl ether (solubility ratio 0.95) was compared in five dogs. A larger difference between the elimination of the two gases was observed than predicted from the differences in molecular weight. The observed individual gas effect appears to be diffusion related, influenced both by the molecular weight of a gas and its erythrocyte-plasma partition coefficient ratio.

Acetylene↗