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Biomedical subjects

S J Day

Publications and source records attributed to S J Day.

At least 19 recordsLinked to original sources

Sample size estimation for comparing two or more treatment groups in clinical trials.

Methods for estimating required sample size for comparing two population means have been published. Most involve the use of complicated formulae and tables. These methods are limited to comparing two groups. Although techniques exist to determine sample sizes for comparing more than two groups, they are intrinsically far more complicated. A simple linear nomogram is proposed as a solution to these problems, and its use is illustrated with examples of parallel group, ordered parallel group and factorial designs.

Algorithms

Diagnosis of motor neuron disease by neurologists: a study in three countries.

Ninety four neurologists in the United Kingdom, China, and West Germany responded to two structured questionnaires. The first assessed the diagnostic weighting assigned to a number of symptoms, signs, and clinical investigations ascertained from classical descriptions and case notes of patients with motor neuron disease (MND). The second tested the likelihood and consistency of diagnosis in a series of case summaries representing the clinical data of 10 patients with clinically and pathologically documented motor neuron disease. There was a wide measure of agreement concerning the common clinical features of the disease, especially regarding fasciculation of the tongue, fasciculation associated with weakness seen in more than one limb, and dysphagia. In the case summaries, however, there was clear variation in the ranked likelihood of the diagnosis of MND and in the consistency of diagnostic behaviour in the different groups of neurologists. These findings support the need for internationally agreed criteria in the diagnosis of MND. Any such criteria will need to be tested against a standardised data set to establish their validity.

China

Inter- and intraindividual variation in pressure-volume relations of the rectum in normal subjects and patients with the irritable bowel syndrome.

The relation between intrarectal volume and pressure during increasing rectal distension by a latex balloon were studied on repeated occasions in 10 healthy adult volunteers to define variations within and between individuals. A wide intersubject variation in the maximum tolerable volume (58-908 ml) and pressure (12.2-108.8 cm H2O) at this end point was seen, and these two values were correlated (r = 0.78). Intrasubject variation in maximum tolerable volume also occurred which was related to study order and progressively reduced with repeated study. In 26 unselected patients with pain predominant irritable bowel syndrome similar intersubject variation was noted and virtually all patients data fell within the calculated 95% confidence limits of the normal individuals. Differentiation between patients and normal subjects was not possible from knowledge of rectal responses. These noticeable inter- and intrasubject variations in rectal responses to distension need to be considered whenever similar techniques are proposed for use in the study of rectal disease or of rectal response to treatment.

Adolescent

An investigation of factors influencing the longevity of restorations in primary molars.

The treatment records of three dentists working in south-east England were screened and 361 chosen for the investigation of the longevity of restorations placed in primary molars. The analysis was carried out using an independent sampling technique, i.e., one restoration per patient. The median survival time for all the restorations was 70.6 months (standard error +/- 3.7 months). The survival pattern of the restorations for the three dentists was different and therefore the influence of six factors on the life-span of restorations was investigated using the Cox regression model. There was no evidence that the life-span of the restorations depended on the sex of the patients (p = 0.506), or the type of primary molars being treated (p = 0.776); there was weak evidence that the life-span depended on the caries susceptibility of the patient (p = 0.151) and preformed metal crown restorations (p = 0.106); there was good evidence that the life-span depended on the age of the patients at the time of treatment (p = 0.016), whether pretreatment radiographs had been taken (p = 0.023) and type of amalgam restoration (p = 0.003).

Child

Sample size and power for comparing two or more treatment groups in clinical trials.

Methods for determining sample size and power when comparing two groups in clinical trials are widely available. Studies comparing three or more treatments are not uncommon but are more difficult to analyse. A linear nomogram was devised to help calculate the sample size required when comparing up to five parallel groups. It may also be used retrospectively to determine the power of a study of given sample size. In two worked examples the nomogram was efficient. Although the nomogram offers only 5% and 1% significance levels and can be used only for up to five treatment groups, this is sufficient for most researchers.

Analysis of Variance

Glycopyrronium requirements for antagonism of the muscarinic side effects of edrophonium.

We have compared, in 60 adult patients, the cardiovascular effects of glycopyrronium 5 micrograms kg-1 and 10 micrograms kg-1 given either simultaneously or 1 min before edrophonium 1 mg kg-1. Significant differences between the four groups were detected (P less than 0.001). Both groups receiving 10 micrograms kg-1 showed increases in heart rate of up to 30 beat min-1 (95% confidence limits 28-32 beat min-1). Use of glycopyrronium 5 micrograms kg-1 provided greater cardiovascular stability and, given 1 min before the edrophonium, was sufficient to minimize early, edrophonium-induced bradycardias. This low dose of glycopyrronium provided good control of oropharyngeal secretions.

Adult

Life-span of amalgam restorations in primary molars: some results and comments on statistical analyses.

The life-span of amalgam restorations placed in primary molars by three general dental practitioners is investigated. Two methods of analysis have been carried out. In the analysis of "non-independent" restorations (i.e. using several restorations from each mouth), the median survival time was 52.8 months with an apparent standard error of 2.1 months. In the analysis of "independent" restorations (i.e. only using one restoration from each mouth), three random samples were chosen and their median survival times were 68.2 months (s.e. = 6.9), 60.5 months (s.e. = 6.9), and 56.8 months (s.e. = 3.7). The two methods are compared and discussed. It is concluded that the analysis of "independent" restorations should be the method of choice in studying the life-span of restorations.

Actuarial Analysis

Perturbation of upper gastrointestinal transit and antroduodenal motility by experimentally applied stress: the role of beta-adrenoreceptor mediated pathways.

A series of three experiments were performed on healthy adult volunteers to investigate the possible role played by beta-adrenoreceptor mediated pathways in the disturbance of human upper intestinal motor function by hand immersion in cold water. In the first experiment, (an extended pilot study on one individual), orocaecal transit of a standard meal was measured on 36 occasions with and without cold water stimulation and with and without a series of alpha and beta blocking drugs. Cold water stimulation consistently delayed transit in this individual, an effect which was attenuated by prior beta-blockade. In a double blind trial of the effect of beta-blocker atenolol v placebo on transit in nine individuals, a consistent reduction in the cold water induced transit delay was observed (p less than 0.01) independent of any direct effect of beta-blockade. In the third experiment seven individuals underwent repeated studies of antroduodenal pressure activity comparing the effects of cold and warm water stimulation with and without beta blockade to determine whether the observed transit effect could be related to an action on gastrointestinal motility. Cold water stimulation reduced antroduodenal motility, but no consistent effects of previous beta blockade were noted. These studies indicate the presence of a beta-adrenoreceptor mediated pathway in the cold water induced delay of orocaecal transit but not in the inhibition of gastroduodenal motility. Further studies are indicated to determine the site and mode of action of this transit effect more precisely.

Adolescent

Comparative quality assessment in immunocytochemistry: pilot study of CD15 staining in paraffin wax embedded tissue in Hodgkin's disease.

The feasibility of comparative quality assessment studies in immunocytochemistry was examined. The reactions of three CD15 antibodies--anti-Leu M1, DM1, and Tü9--were examined in paraffin wax sections in Hodgkin's disease under a variety of different fixation and pre-treatment conditions, using four immunochemical detection techniques. All three antibodies stained Reed-Sternberg cells, but DM1 could be used at slightly higher dilutions to achieve comparable results. Tissue fixed in formol sublimate showed the most intense staining reactions, and formol saline and neutral buffered formalin gave relatively poor results. Although neuraminidase pre-treatment improved staining, its routine use is probably contraindicated by its high cost. Trypsinisation has some value for sections of tissue fixed in formol saline and neutral buffered formalin. The avidin-biotin complex technique produced the best results, but indirect immunoperoxidase produced acceptable results, is technically easier to perform, and is less expensive. It is concluded that information regarding variations in techniques and commercially available reagents, which may be of use in routine diagnostic histopathology, can be obtained by comparative quality assessment studies of this type.

Adult

Optimal placebo response rates for comparing two binomial proportions.

This paper considers the problem of comparing proportions in clinical trials where two parallel groups are studied. The question of what will happen to the response rate of an active therapy if some external factor affects the placebo rate is asked and two different, but similar, answers are proposed. Assuming either a logistic or probit model has substantial influence on the sample size required to detect differences and optimal comparisons are suggested. The idea is illustrated by a clinical trial of treatment for peptic ulcer and suggestions for other possible applications are presented.

Acne Vulgaris

Factors associated with joint mobility in an adolescent population.

Fixed torque devices were used to measure joint mobility at three sites in 364 adolescents including 39 families with at least two siblings. Increasing age and being male were associated with reduced laxity, and a strong effect of family was observed in the 39 sibling sets studies. The population included 47 Asians whose mobility was similar to that of the non-Asians, though the female/male difference was apparently greater in the former group. None of the above conclusions apply to index finger hyperextension, and it is apparent that genetic and constitutional factors only affect mobility at some sites. Such observations could lead to a review of current scoring systems for clinical hypermobility.

Adolescent

Motor responses of the oesophagus to intraluminal distension in normal subjects and patients with oesophageal clearance disorders.

Oesophageal motor responses to intraluminal distension were studied manometrically in 16 healthy volunteers and in nine patients with disordered swallowing, who had prolonged oesophageal clearance without structural abnormality. In the normal subjects distension was associated with an increased number of secondary contractions above the balloon, decrease of all contractile activity below the balloon and was accompanied by an aborally propulsive force which occurred independently of the perception of discomfort. Cholinergic blockade abolished the proximal distension induced contractile response, but did not affect primary peristalsis. Despite normal sensory thresholds, proximal excitatory responses to distension were absent in six and distal inhibition was absent in seven patients. These results show that the normal human oesophagus responds to distension with a proximal enhancement of propulsive motor activity, mediated through a cholinergic pathway. This may be defective in some patients with disordered oesophageal transit. Investigation of the motor responses to intraluminal distension may thus be a useful adjunct to standard manometry for studying patients with suspected oesophageal clearance dysfunction and might allow identification of disordered enteric nervous control.

Adult

Motor responses of the small intestine to intraluminal distension in normal volunteers and a patient with visceral neuropathy.

The motor responses of the small intestine to intraluminal distension were studied proximal and distal to an inflatable balloon in 13 normal volunteers. During fasting, distension rapidly induced a persistent localised inhibition of distal contractile activity with a small proximal increase. Proximally, phase III activity was unaffected during distension but its propagation across and appearance below the balloon was inhibited. Upon deflating the balloon a normal motor pattern rapidly returned. Similar changes were observed during distension in the fed state. The changes in the motor pattern resemble those of the intrinsically mediated 'peristaltic reflex', studied in animals, and suggest that in man the response to balloon distension may also be mediated through an intrinsic mechanism. A patient with a visceral neuropathy, studied in a similar manner, had no inhibition of distal motor activity during distension, suggesting a functional defect of the enteric nerves. Further observations of the motor responses to distension in similar patients seem indicated to determine the usefulness of this technique for evaluating enteric nervous system function when an abnormality is suspected.

Adult