Showing papers by "Clinical Trial Service Unit published in 1996"

Mortality from smoking worldwide

Abstract: Estimates are made of the numbers and proportions of deaths attributable to smoking in 44 developed countries in 1990. In developed countries as a whole, tobacco was responsible for 24% of all male deaths and 7% of all female deaths, rising to over 40% in men in some former socialist economies and 17% in women in the USA. The average loss of life for all cigarette smokers was about 8 years and for those whose deaths were attributable to tobacco about 16 years. Trends in mortality attributable to tobacco differed between countries. In some the mortality in middle age (35-69 years) had decreased by half in men since 1965; in others it was continuing to increase. In women, the proportion was mostly increasing, almost universally in old age. Mortality not attributable to smoking decreased since 1955 in all OECD (Organization for European Collaboration and Development) countries, by up to 60% in men and more in women. No precise estimate can be made of the number of deaths attributable to smoking in undeveloped countries, but the prevalence of smoking suggests that it will be large. In the world as a whole, some 3 million deaths a year are estimated to be attributable to smoking, rising to 10 million a year in 30-40 years' time.

Clinical effects of anticoagulant therapy in suspected acute myocardial infarction: systematic overview of randomised trials.

Abstract: Objectives: Most randomised trials of anticoagulant therapy for suspected acute myocardial infarction have been small and, in some, aspirin and fibrinolytic therapy were not used routinely. A systematic overview (meta-analysis) of their results is needed, in particular to assess the clinical effects of adding heparin to aspirin. Design: Computer aided searches, scrutiny of reference lists, and inquiry of investigators and companies were used to identify potentially eligible studies. On central review, 26 studies were found to involve unconfounded randomised comparisons of anticoagulant therapy versus control in suspected acute myocardial infarction. Additional information on study design and outcome was sought by correspondence with study investigators. Subjects: Patients with suspected acute myocardial infarction. Interventions: No routine aspirin was used among about 5000 patients in 21 trials (including half of one small trial) that assessed heparin alone or heparin plus oral anticoagulants, and aspirin was used routinely among 68 000 patients in six trials (including the other half of one small trial) that assessed the addition of intravenous or high dose subcutaneous heparin. Main outcome measurements: Death, reinfarction, stroke, pulmonary embolism, and major bleeds (average follow up of about 10 days). Results: In the absence of aspirin, anticoagulant therapy reduced mortality by 25% (SD 8%; 95% confidence interval 10% to 38%; 2P = 0.002), representing 35 (11) fewer deaths per 1000. There were also 10 (4) fewer strokes per 1000 (2P = 0.01), 19 (5) fewer pulmonary emboli per 1000 (2P Conclusions: The clinical evidence from randomised trials does not justify the routine addition of either intravenous or subcutaneous heparin to aspirin in the treatment of acute myocardial infarction (irrespective of whether any type of fibrinolytic therapy is used). Key messages Heparin seemed to be useful among patients with suspected acute myocardial infarction who, in the past, had received neither aspirin nor fibrinolytic therapy The available evidence from clinical trials does not justify the routine addition of intravenous or subcutaneous heparin to aspirin in the treatment of acute myo- cardial infarction (whether or not any type of fibrinolytic therapy is used)

Cancers weakly related to smoking

Abstract: In 1985, review of the carcinogenic effects of tobacco led the International Agency for Research on Cancer to conclude that the smoking of cigarettes was an important cause of cancers of the lung, larynx, oro- and hypo-pharynx, oesophagus, bladder, renal pelvis, and pancreas and that the smoking of tobacco in other form was also an important cause of some of them. More evidence about common cancers has now been obtained in cohort studies and about less common cancers in case-control studies. Many are weakly related to smoking. Review now justifies the conclusion that cigarette smoking is also a cause of cancers of the stomach, renal body, liver, and nose and of myeloid leukaemia and may be a cause of cancers of the nasopharynx and lip, and that pipe smoking is a cause of cancer of the lip. Associations between cigarette smoking and cancers of the large bowel and cervix uteri may be largely, and perhaps wholly, explained by confounding.

Nature and nurture: possibilities for cancer control.

Abstract: Nature and nurture interact and in most cases it is impossible to specify quantitatively the contribution of either to the causation of a disease. Only rarely is either neutral in the sense that the other accounts for all the variation in risk. It seems unlikely that more than a few per cent of all cancers will be accounted for by inherited susceptibility with a high penetrance and a neutral environment. Small variations in susceptibility may, however, be associated with different genetic alleles that will facilitate focused measures of prevention and perhaps provide a lead to causation. For the practical control of most cancers we must intervene by treatment or prevention. Knowledge of the variation in the incidence of cancers suggests that age-specific incidence rates could be reduced by 80-90%, half by the application of existing knowledge. The possibilities of control by prevention are discussed under the headings of tobacco smoke, alcohol, infection, diet, physical activity, reproduction, medicines and medical procedures, and occupation and pollution. In conclusion, attention is drawn to eight types of cancer that have become more common in the UK in the last 25 years, some of which we do not know how to prevent and which require urgent research.

Dose intensification in acute myeloid leukaemia: greater effectiveness at lower cost. Principal report of the Medical Research Council's AML9 study. MRC Leukaemia in Adults Working Party.

Abstract: Between 1984 and 1990, 972 patients aged 1-79 years with acute myeloid leukaemia (AML), from 85 British hospitals, were entered into the MRC's 9th AML trial. Patients were randomized between DAT 1 + 5 (daunorubicin for 1 d, with cytarabine and 6-thioguanine for 5 d) and DAT 3 + 10 (same dose drugs for 3 and 10 d respectively) as induction therapy. The 63% who achieved complete remission (CR) were randomized to receive two courses of DAT 2 + 7 alternating with two courses of either MAZE (m-AMSA, 5-azacytidine, etoposide) or COAP (cyclophosphamide, vincristine, cytarabine, prednisone). Finally, those still in CR were randomized to receive either 1 year of maintenance treatment with eight courses of cytarabine and thioguanine followed by four courses of COAP, or no further cytotoxic therapy. Resistance to induction therapy was less common with the DAT 3 + 10 regimen than with DAT 1 + 5 (13% v 23%; P = 0.0001) and hence, despite a 5% increase in the risk of induction death, the CR rate was higher (66% v 61%; P = 0.15). Moreover, CR was achieved more rapidly with DAT 3 + 10 (median 34 v 46 d; P < 0.0001) and thus patients required less time in hospital (mean 20 v 29 d) and less blood product support. 5-year relapse-free survival (28% v 23%; P = 0.05) and survival (23% v 18%; P < 0.05) were also better with DAT 3 + 10. Post-remission intensification of therapy with MAZE resulted in fewer relapses (66% v 74% at 5 years; P = 0.03) but patients allocated MAZE required considerably more supportive care and 14 (4.5%) died following 312 MAZE courses, whereas no deaths occurred following COAP. 5-year survival was not significantly higher with MAZE (37% v 31%). Finally, although 1 year of outpatient maintenance treatment appeared to delay, but not prevent, recurrence it did not improve 5-year survival which was non-significantly worse for those allocated maintenance treatment (41% v 44%). We conclude that the more intensive induction regimen, DAT 3 + 10, is not only more effective than DAT 1 + 5, even for older patients, but is also less expensive; intensive post-remission therapy with MAZE achieves better leukaemic control but at the cost of substantial toxicity; whereas low-level maintenance therapy confers no apparent advantage in survival as well as being inconvenient and costly.

Tobacco--the growing epidemic in China.

Abstract: Worldwide, 30 million adults died in 1990, 3 million from the effects of smoking tobacco, 1-3 and the annual number of deaths from tobacco use is increasing. By about 2025, when the children of today reach middle age, some 10 million a year will die from the effects of tobacco. 2 The increase is predicted to be sharpest (from 1 million in 1995 to 7 million in 2025) in developing countries, of which China is the largest and consumes the most tobacco. In early middle age, about 5% of women and 75% of men in China are occasional or daily smokers. 4 Chinese men number 10% of the adults in the world, but smoke about 30% of the world's cigarettes. 4 Thus far, few Chinese women smoke, except in Manchuria, but among Chinese men, cigarette smoking has recently increased substantially (1 cigarette per day in 1952, See also p 1646.

A modular questionnaire for the assessment of longterm quality of life in leukaemia patients: The MRC/EORTC QLQ-LEU

Abstract: We describe the psychometric analysis of a supplementary quality of life measure (MRC/EORTC QLQ-LEU) for evaluating long term sequelae of leukaemia treatments. The questionnaire under development was administered to 388 patients entered into the EORTC-GIMEMA AML 8A and the MRC AML10 clinical trials who were in complete remission for at least one year after completion of treatment on these trials. Results indicated a measure which is useful in evaluating the long-term effects of treatment in relation to chronic graft-vs-host disease and infection susceptibility. The performance of this measure in terms of its sensitivity and specificity between treatment arms was established by comparisons between the three treatment modalities in the above-mentioned trials and is the subject of further investigation. The new Leukaemia Module can be recommended for use alongside generic QOL instruments as a measure of long-term quality of life in leukaemia trials.

The retinoblastoma gene (rb1) in acute myeloid leukaemia: analysis of gene rearrangements, protein expression and comparison of disease outcome.

Abstract: The occurrence of retinoblastoma gene abnormalities in a large subset of various malignancies suggests an important role for this tumour suppressor gene in carcinogenesis, but this varies considerably from one tumour type to another and results in patients with acute myeloid leukaemia (AML) have been controversial. We analysed 106 AML patients and 18 normal controls for RB1 gene rearrangements and 86 AML patients for RB protein (pRB) expression. Southern blot analysis detected no gross gene rearrangements, but several restriction enzyme polymorphisms were observed. By Western blot analysis, 20 patients (23%) had no detectable pRB protein and seven (8%) had truncated pRB bands. Discordance between the DNA and protein data suggests that there may be minor deletions and point mutations in the RB1 gene or abnormalities in the proteins regulating the expression of pRB. No significant differences in the frequency of attainment of complete remission or length of survival were observed between patients with normal and abnormal pRB.

Absence of effects of prolonged simvastatin therapy on nocturnal sleep in a large randomized placebo-controlled study

Abstract: 1It has been suggested that lipophilic HMG CoA reductase inhibitors, like lovastatin and simvastatin, may cause sleep disturbance. 2Six hundred and twenty-one patients at increased risk of coronary heart disease were randomized in a single centre to receive 40 mg daily simvastatin, 20 mg daily simvastatin or matching placebo. To assess the effects of prolonged use of simvastatin on nocturnal sleep quality and duration, a sleep questionnaire was administered to 567 patients (95% of 595 survivors) at an average of 88 weeks (range: 44–129 weeks) after randomization. 3The main outcome measures were sleep-related problems and use of sleep-enhancing medications reported during routine study follow-up visits, and responses to the sleep questionnaire about changes in sleep duration and about various sleep events during the preceding month. 4No differences were observed between the treatment groups in the frequency of sleep-related problems reported, in the proportion of follow-up visits at which such problems were reported, or in the use of sleep-enhancing medications. The numbers who stopped study treatment were similar in the different treatment groups, and no patient stopped principally because of insomnia. In response to the sleep questionnaire, there were no significant differences between the treatment groups in reports of various sleep events during the preceding month, except that slightly fewer patients allocated simvastatin reported waking often. No differences in sleep duration were observed. 5This placebo-controlled trial does not indicate any adverse effects of prolonged treatment with simvastatin on systematically sought measures of sleep disturbance.

Absence of effects of prolonged simvastatin therapy on nocturnal sleep in a large randomized placebo-controlled study. Oxford Cholesterol Study Group.

Abstract: 1It has been suggested that lipophilic HMG CoA reductase inhibitors, like lovastatin and simvastatin, may cause sleep disturbance. 2Six hundred and twenty-one patients at increased risk of coronary heart disease were randomized in a single centre to receive 40mg daily simvastatin, 20mg daily simvastatin or matching placebo. To assess the effects of prolonged use of simvastatin on nocturnal sleep quality and duration, a sleep questionnaire was administered to 567 patients (95% of 595 survivors) at an average of 88 weeks (range: 44–129 weeks) after randomization. 3The main outcome measures were sleep-related problems and use of sleep-enhancing medications reported during routine study follow-up visits, and responses to the sleep questionnaire about changes in sleep duration and about various sleep events during the preceding month. 4No differences were observed between the treatment groups in the frequency of sleep-related problems reported, in the proportion of follow-up visits at which such problems were reported, or in the use of sleep-enhancing medications. The numbers who stopped study treatment were similar in the different treatment groups, and no patient stopped principally because of insomnia. In response to the sleep questionnaire, there were no significant differences between the treatment groups in reports of various sleep events during the preceding month, except that slightly fewer patients allocated simvastatin reported waking often. No differences in sleep duration were observed. 5This placebo-controlled trial does not indicate any adverse effects of prolonged treatment with simvastatin on systematically sought measures of sleep disturbance.