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Biomedical subjects

D G Cook

Publications and source records attributed to D G Cook.

142 records · Page 8Linked to original sources
PubMed1985

Is the clinical trial evidence about new drugs statistically adequate?

The statistical adequacy of all papers published in the period 1976-80 describing clinical trials of five non-steroidal anti-inflammatory and two analgesic drugs introduced into the UK market in 1978 and 1979 has been assessed using a checklist of simple criteria. Most trials were reported to be randomised and double-blind. Trial designs were less satisfactory in other important respects; the sample size of most trials was inadequate to demonstrate superiority of the new drug compared with an active control therapy. The period of treatment assessment was short in view of the likelihood of prolonged prescription of drugs in these classes. It is suggested that licensing authorities should demand higher standards of clinical trial evidence offered in support of new drugs.

Anti-Inflammatory Agents↗
PubMed1984

A case of envenomation by the neotropical colubrid snake, Stenorrhina freminvillei.

The case history of a bite by the neotropical opisthoglyph, Stenorrhina freminvillei, is presented. This is apparently the first documentation of human envenomation by this genus. Localized pain and swelling were the predominant symptoms; no systemic reaction was noted. Such mild effects are consistent with the bites reported for other New World colubrids, in contrast to the potentially lethal effects produced by Old World colubrid genera Dispholidus, Thelotornis, Rhabdophis and Atractaspis.

Animals↗
PubMed1984

Prevalence of ischaemic heart disease in middle aged British men.

The prevalence of ischaemic heart disease was determined by an administered questionnaire and electrocardiography in 7735 men aged 40-59 years drawn at random from general practices in 24 British towns. Overall, one quarter of these men had some evidence of ischaemic heart disease on questionnaire or electrocardiogram or both. On questionnaire, 14% of men had possible myocardial infarction or angina, with considerable overlap of the two syndromes. The prevalence of possible myocardial infarction combined with angina and of definite angina only showed a fourfold increase over the age range studied. Electrocardiographic evidence of ischaemic heart disease (definite or possible) was present in 15% of men, there being myocardial infarction in 4.2% and myocardial ischaemia in 10.3%. Electrocardiographic evidence of myocardial infarction increased fourfold over the age range studied. There was considerable overlap of questionnaire and electrocardiographic evidence of ischaemic heart disease. Nevertheless, more than half of those with possible myocardial infarction combined with angina had no resting electrocardiographic evidence of ischaemic heart disease, and half of those with definite myocardial infarction on electrocardiogram had no history of chest pain at any time. This national population based study strongly suggests that the prevalence of ischaemic heart disease in middle aged British men is greater than has been indicated by previous studies based on occupational groups.

Adult↗
PubMed1984

Recall of diagnosis by men with ischaemic heart disease.

In a study of the prevalence of ischaemic heart disease in middle aged men in 24 British towns, the subjects were asked whether a doctor had ever told them that they had any form of cardiovascular disease. Their recall of various diagnoses was related to evidence of ischaemic heart disease obtained by an administered questionnaire on chest pain and electrocardiography. Twenty one per cent of men recalled a diagnosis of cardiovascular disease, in one quarter of whom it was ischaemic heart disease. There was a sixfold increase in the prevalence of recall of a diagnosis of ischaemic heart disease over the age range studied. Only one third of the men with possible myocardial infarction on questionnaire recalled such a diagnosis having been made by a doctor. Only half of those with a definite myocardial infarction on an electrocardiogram could recall a diagnosis of ischaemic heart disease. Even in severe (grade 2) angina 40% could not recall being told that they had heart disease. Overall, only one in five of those regarded as having ischaemic heart disease was able to recall such a diagnosis having been made by a doctor, and these were likely to be those most severely affected. Ischaemic heart disease is common in middle aged British men, but most of those affected are apparently not aware of their condition. This low level of awareness among patients and doctors may contribute to a lack of public concern regarding the need for action to reduce the incidence of ischaemic heart disease in Great Britain.

Adult↗
PubMed1983

Multiple regression in geographical mortality studies, with allowance for spatially correlated errors.

In order to provide clues to the aetiology of a disease, mortality indices for different areas are often related to explanatory variables by using multiple regression. However, mortality in nearby areas may be similar for reasons not attributable to the covariates, so the errors will not be independent. This paper suggests a way of finding a parameterized form for the correlated error structure by examining the residuals from an ordinary least squares regression. Such a model is then fitted by using maximum likelihood. An example based on cardiovascular mortality in British towns is used to illustrate the problem and our solution.

Cardiovascular Diseases↗
PubMed1983

Role of habituation and classical conditioning in the development of morphine tolerance.

Rats were tested for the development of analgesic tolerance to low (5 mg/kg) and high (15 mg/kg) doses of morphine once every 12 or 48 hr in distinctive or nondistinctive environments. Results indicated that in a nondistinctive environment, development of analgesic tolerance to morphine (a) is a function of repeated presentation of morphine, (b) is more rapid with massed than with spaced presentations of morphine, (c) is not dependent on variation in drug levels, (d) shows spontaneous recovery across time, and (e) is not sensitive to marked alteration in the environment. It is suggested that in nondistinctive environments the development of tolerance to morphine is mediated by a habituation process. Results show that in a distinctive environment development of analgesic tolerance to morphine (a) is a function of repeated presentation of morphine, (b) is slightly more rapid with spaced than with massed presentations of morphine, (c) is not dependent on variation in drug levels, (d) shows persistence across time, and (e) is sensitive to alteration in the environment. It is suggested that in a distinctive environment the development of tolerance to morphine is mediated by a classical conditioning process that is superimposed on the habituation process.

Animals↗
PubMed1983

Mothers' intentions and the immunization of their infants.

One hundred and seventy-eight mothers who had recently been delivered were interviewed before discharge from hospital to ascertain their initial intentions about vaccination of their children. Nine months later the behaviour of 154 mothers was checked from health service records; 24 were lost to follow-up.One hundred and forty-one (92 per cent) of the infants had received at least one dose of vaccine against polio, diphtheria and tetanus. Eighty-five infants (63 per cent of 135) had received at least one dose of vaccine against whooping-cough; 19 mothers had been advised against the vaccine. Failure to have their children vaccinated against whooping-cough correlated with the mothers' initial intentions, although a high proportion of mothers who were initially against the vaccine had started vaccination by the time their child was nine months old. Mothers attending general practitioners were more likely to have their infants vaccinated against whooping-cough than those attending community health clinics, and this difference was not explained by the social characteristics of the mothers nor by more positive early intentions among the mothers who attended general practitioners.

Adult↗
PubMed1982

Health of unemployed middle-aged men in Great Britain.

The frequencies of several factors, including major physical disease, in employed and unemployed men enrolled in the British Regional Heart Study (BRHS) have been compared. The BRHS is a prospective study of cardiovascular disease in middle-aged men selected at random from general practices in twenty-four towns. The unemployed group was subdivided into those who said they were unemployed because of ill-health and those who regarded their unemployment as not due to illness. The ill unemployed reported a much higher rate of doctor-diagnosed illnesses than the not-ill unemployed or the employed. The frequencies of bronchitis, obstructive lung disease, and ischaemic heart disease were higher in the unemployed than the employed, with the highest rates in the ill unemployed. The frequency of hypertension was the same in employed and unemployed men. Cigarette smoking and heavy drinking were apparently more common among the unemployed, but after adjustment for social class and town of residence only smoking was slightly higher among the unemployed. Use of tranquillisers was three to four times more common in the ill unemployed than in the not-ill unemployed or the employed. In this study, the unemployed had far more chronic physical illnesses than the employed, whether or not the employed men regarded themselves as ill. Studies of the health consequences of unemployment must allow for the pre-existing state of health, and evidence on the state of health cannot rely solely on self-reporting of illness.

Adult↗
PubMed1982

Tranquillizer use in middle-aged British men.

We have examined the use of tranquillizers by 7,735 middle-aged men currently enrolled in the British Regional Heart Study, a prospective study of cardiovascular disease in 24 towns throughout Great Britain. Tranquillizer use was reported by 620 men (8 per cent). There was a slightly greater prevalence of tranquillizer use in the older men and the non-manual workers. Men with physical disease diagnosed by their doctor or by objective measurements during the study were more likely to be using tranquillizers than men with no physical disease. This was most evident for ischaemic heart disease, however diagnosed, and for hypertension diagnosed by their doctors. There was an inverse relationship between drinking and tranquillizer usage: heavy drinkers had lower rates of usage. There was no association between tranquillizer use and smoking habits.This study indicates that tranquillizer use in these middle-aged men is little influenced by age, social class or smoking, but that there is a strong, positive association between tranquillizer use and the presence of doctor-diagnosed physical disease. While our data provide support for the suggestion that alcohol and tranquillizers may be used interchangeably by some individuals, this finding could also be an outcome of doctors' and patients' awareness of the undesirable effects of combining alcohol and tranquillizers.

Adult↗
PubMed1981

D-penicillamine treatment improves survival in primary biliary cirrhosis.

The copper-chelating, immunological, and antifibrotic effects of D-penicillamine indicated that it might be suitable for the treatment of primary biliary cirrhosis (PBC). In a randomised clinical trail, 55 PBC patients received penicillamine (600 mg daily), and 32 received a placebo. Drug reactions developed in 16 patients on penicillamine. All deaths occurred in patients with stage 3 or 4 (late stage) liver histology on entry to the study. 5 (14%) of 37 penicillamine-treated patients and 10 (43%) of 23 placebo patients have died (p less than 0.01). Improvement in survival only became evident after 18 months. Survivors in the penicillamine group demonstrated a significant fall in serum aspartate transaminase, serum immunoglobulins, and liver copper concentrations. On follow-up liver biopsy 12-72 months (median 33) after joining the study, 21% of penicillamine-treated patients had less pronounced inflammation and piecemeal necrosis, whereas there had been no improvement in patients on placebo (p less than 0.02). Penicillamine did not retard the histological evolution of the liver disease from the early prefibrotic stages to the late fibrotic or cirrhotic stages. Both the copper-chelating and immunological effects of penicillamine are probably important in improving survival. The excellent prognosis of patients with PBC in its early histological stages, and the failure of penicillamine to prevent histological progression from early to late stages, suggests that penicillamine treatment should not be given to patients with PBC in the early (stage 1 or 2) histological phase of the disease. Penicillamine treatment is recommended in patients once liver biopsy has demonstrated histological results typical of late stage 3 or 4 PBC.

Antigen-Antibody Complex↗
PubMed1981

Regression of area mortality rates on explanatory variables: what weighting is appropriate?

"One can often gain insight into the aetiology of a disease by relating mortality rates in different areas to explanatory variables. Multiple regression techniques are usually employed, but unweighted least squares may be inappropriate if the areas vary in population size. Also, a fully weighted regression, with weights inversely proportional to binomial sampling variances, is usually too extreme. This paper proposes an intermediate solution via maximum likelihood which takes account of three sources of variation in death rates: sampling error, explanatory variables and unexplained differences between areas. The method is also adapted for logit (death rates), standardized mortality ratios (SMRs) and log (SMRs). Two [United Kingdom] examples are presented."

Demography↗
PubMed1980

British Regional Heart Study: geographic variations in cardiovascular mortality, and the role of water quality.

In a study of regional variations in cardiovascular mortality in Great Britain during 1969-73 based on 253 towns the possible contributions of drinking water quality, climate, air pollution, blood groups, and socioeconomic factors were evaluated. A twofold range in mortality from stroke and ischaemic heart disease was apparent, the highest mortality being in the west of Scotland and the lowest in south-east England. A multifactorial approach identified five principal factors that substantially explained this geographic variation in cardiovascular mortality-namely, water hardness, rainfall, temperature, and two social factors (percentage of manual workers and car ownership). After adjustment for other factors cardiovascular mortality in areas with very soft water, around 0.25 mmol/l (calcium carbonate equivalent 25 mg/l), was estimated to be 10-15% higher than that in areas with medium-hard water, around 1.7 mmol/l (170 mg/l), while any further increase in hardness beyond 1.7 mmol/l did not additionally lower cardiovascular mortality.Thus a negative relation existed between water hardness and cardiovascular mortality, although climate and socioeconomic conditions also appeared to be important influences. Cross-sectional and prospective surveys of 7500 middle-aged men from 24 towns are in progress and will permit further exploration of these geographic differences, especially with regard to personal risk factors such as blood pressure, blood lipid concentrations, and cigarette smoking.

Adult↗