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Showing papers by "Clinical Trial Service Unit published in 1997"


Journal ArticleDOI
TL;DR: The epidemiological and clinical evidence on CHD and Helicobacter pylori, Chlamydia pneumoniae, and cytomegalovirus, as well as possible mechanisms are reviewed.

1,213 citations


Journal ArticleDOI
11 Jan 1997-BMJ
TL;DR: In this article, a meta-analysis of metabolic ward studies of solid food diets in healthy volunteers was conducted to determine the quantitative importance of dietary fatty acids and dietary cholesterol to blood concentrations of total, low density lipoprotein, and high density LDL cholesterol.
Abstract: OBJECTIVE: To determine the quantitative importance of dietary fatty acids and dietary cholesterol to blood concentrations of total, low density lipoprotein, and high density lipoprotein cholesterol. DESIGN: Meta-analysis of metabolic ward studies of solid food diets in healthy volunteers. SUBJECTS: 395 dietary experiments (median duration 1 month) among 129 groups of individuals. RESULTS: Isocaloric replacement of saturated fats by complex carbohydrates for 10% of dietary calories resulted in blood total cholesterol falling by 0.52 (SE 0.03) mmol/l and low density lipoprotein cholesterol falling by 0.36 (0.05) mmol/l. Isocaloric replacement of complex carbohydrates by polyunsaturated fats for 5% of dietary calories resulted in total cholesterol falling by a further 0.13 (0.02) mmol/l and low density lipoprotein cholesterol falling by 0.11 (0.02) mmol/l. Similar replacement of carbohydrates by monounsaturated fats produced no significant effect on total or low density lipoprotein cholesterol. Avoiding 200 mg/day dietary cholesterol further decreased blood total cholesterol by 0.13 (0.02) mmol/l and low density lipoprotein cholesterol by 0.10 (0.02) mmol/l. CONCLUSIONS: In typical British diets replacing 60% of saturated fats by other fats and avoiding 60% of dietary cholesterol would reduce blood total cholesterol by about 0.8 mmol/l (that is, by 10-15%), with four fifths of this reduction being in low density lipoprotein cholesterol.

563 citations


Journal ArticleDOI
TL;DR: Which of these treatments have been shown to improve survival and other major clinical outcomes in patients with suspected acute myocardial infarction are reviewed to determine.
Abstract: In this article, we review the randomized clinical trials of aspirin, of heparin, and of fibrinolytic therapy in patients with suspected acute myocardial infarction to determine which of these treatments have been shown to improve survival and other major clinical outcomes. Aspirin Benefits of Aspirin during and after Suspected Myocardial Infarction The Second International Study of Infarct Survival (ISIS-2) demonstrated conclusively the substantial value of aspirin therapy in patients with suspected acute myocardial infarction1 (and other studies have shown the value of aspirin in patients with unstable angina2). In the ISIS-2 trial, assignment to one month of treatment with . . .

279 citations


Journal ArticleDOI
12 Nov 1997-JAMA
TL;DR: Cigarette smoking is already a major cause of death in China, and among middle-aged Shanghai men, about 20% of all deaths during the 1980s were due to smoking, which was greatest among men who began smoking before the age of 25 years.
Abstract: Context. —In recent decades, there has been a rapid and substantial increase in tobacco consumption in China, particularly by men, but little is known from local epidemiologic studies about the pattern of smoking-related deaths. Objective. —To assess the current health effects of cigarette smoking in Shanghai, China. Design. —Prospective observational study of mortality in relation to cigarette smoking. Setting. —Eleven factories in urban Shanghai. Subjects. —A total of 9351 adults (6494 men and 2857 women) aged 35 to 64 years at baseline survey during the 1970s. Outcome Measures. —All-cause and cause-specific mortality. Results. —During an average follow-up of 16 years, 881 men and 207 women died. Among men, 61% had described themselves as current cigarette smokers at baseline, and their overall mortality was significantly greater than that of nonsmokers (relative risk [RR], 1.4; 95% confidence interval [CI], 1.2-1.7;P Conclusions. —Cigarette smoking is already a major cause of death in China, and among middle-aged Shanghai men, about 20% of all deaths during the 1980s were due to smoking. The excess was greatest among men who began smoking before the age of 25 years, about 47% of whom would, at 1987 mortality rates, die between the ages of 35 and 69 years (compared with only 29% of nonsmokers). These estimates reflect the consequences of past smoking patterns. The future health effects of current smoking patterns are likely to be greater because of the recent large increase in cigarette consumption, particularly at younger ages, in China.

144 citations


Journal ArticleDOI
TL;DR: Almost 12% of all new cases of AML are estimated to have AML1/ETO fusion transcripts and it is suggested that molecular screening should be performed in all cases with the possible exception of the M3 FAB type.
Abstract: Acute myeloid leukaemia (AML) with the t(8;21)(q22;q22) is deemed to be a 'good-risk' disease 396 patients with AML at diagnosis were screened for the presence of t(8;21) and AML1/ETO fusion transcripts by cytogenetic and RT-PCR techniques respectively 32 cases of t(8;21) were detected, all of which were also PCR positive A further 19 cases were detected at the molecular level, predominantly but not exclusively in M1 and M2 FAB types Approximately 12% of all new cases of AML are estimated to have AML1/ETO fusion transcripts and it is suggested that molecular screening should be performed in all cases with the possible exception of the M3 FAB type

107 citations


Journal ArticleDOI
20 Dec 1997-BMJ
TL;DR: It is only in the past 10 years that cardiologists and specialists in preventive medicine have begun to take small or moderate amounts of alcohol seriously, and the evidence for a beneficial effect is now massive.
Abstract: “An ounce of whisky, please Sister,” or was it half an ounce or two ounces? I cannot remember now, but I know that I prescribed some tentatively after having sought the ward sister's opinion when I was called to my first patient with lobar pneumonia as a newly qualified house physician in 1937. There was nothing else to prescribe unless oxygen was needed. In the 19th century alcohol had been prescribed for many debilitating conditions, but its medicinal use was dying out except for people who were terminally ill, and there was certainly no idea that it might be of any use in preventing disease. Some people must have seen Pearl's report in 1926 of a U shaped relation between mortality and the consumption of alcoholic beverages, but it was totally ignored by the medical profession.1 The situation began to change soon after the second world war, with reports of an unusually low prevalence of coronary artery disease in patients found to have cirrhotic livers at necropsy.2 3 Necropsy series were, however, subject to many biases, and these reports excited little interest. Even in the 1970s, when case-control studies of people with and without myocardial infarcts4 and cohort studies of people with different personal characteristics5 began to report a reduced relative risk of myocardial infarction in people who drank small or moderate amounts of alcohol in comparison with non-drinkers, scant attention was paid to them. The belief that alcohol was bad for health was so ingrained that the idea that small amounts might be good for you was hard to envisage, and it is only in the past 10 years that cardiologists and specialists in preventive medicine have begun to take it seriously. The evidence for a beneficial effect is now massive.3 6 7 It …

97 citations


Journal ArticleDOI
TL;DR: Patients who have the inv(16)(p13q22), closely associated with the FAB subtype M4Eo, are deemed to have good‐risk disease and subtle translocation may be difficult to detect in poor‐quality metaphase preparations.
Abstract: It has been established that cytogenetic findings at diagnosis of acute myeloid leukaemia (AML) are a powerful prognostic indicator. Patients who have the inv(16)(p13q22), closely associated with the FAB subtype M4Eo. are deemed to have good-risk disease. This subtle translocation may be difficult to detect in poor-quality metaphase preparations and if missed could lead to the incorrect assignment of risk group and influence further treatment strategies. We studied 321 patients with AML at diagnosis for the presence of inv(16)(p13q22) and CBF beta/MYH11 fusion transcripts by cytogenetic and RT-PCR techniques respectively. Karyotypic analysis detected 21 cases of inv(16) (p13q22), all of which were PCR positive. A further 12 cases were detected at the molecular level only, in FAB types other than M4Eo. The observed frequencies of CBF beta/MYH11 fusion transcripts in our study have been adjusted for the reported incidence of each FAB subtype and we calculate that 10.1% of all new cases of AMLs have molecular evidence of inv(16)(p13q22). only half of which are of the M4Eo subtype. We conclude that molecular screening for the presence of CBF beta/MYH11 fusion transcripts should be mandatory in all case of AML at diagnosis.

91 citations


Journal ArticleDOI
TL;DR: The effects of simvastatin on haemostatic variables appear to be far less marked than its lipid effects, and larger randomized comparisons of the HMG-CoA reductase inhibitors (and of the newer fibrates which may produce greater effects) are needed to provide more reliable estimates of the extent to which they influence these variables.
Abstract: The Oxford Cholesterol Study is a randomized placebo-controlled trial designed primarily to assess the effects of simvastatin on blood cholesterol levels and side-effects in preparation for a large, long-term trial of the effects of cholesterol-lowering drug therapy on mortality. At present there is only limited evidence from randomized comparisons of the effects of HMG-CoA reductase inhibitors, such as simvastatin, on thrombogenic, as distinct from atherogenic, pathways in coronary heart disease. The present sub-study was carried out to assess the effects of simvastatin on a range of haemostatic variables, as well as on free fatty acids and on lipoprotein fractions not studied in detail previously. At an average of about 2 years after starting study treatment, non-fasting blood samples were obtained from a sequential sample of 162 participants who had been randomly allocated to receive 40 mg (54 patients) or 20 mg (57 patients) daily simvastatin or matching placebo treatment (51 patients). Only patients who reported taking their study treatment and who were not known to be diabetic or to be taking some other lipid lowering treatment were to be included. The principal comparisons were to be of those allocated simvastatin (i.e. 20 and 40 mg doses combined) vs those allocated placebo. Among patients allocated simvastatin, marginally significant lower factor VII antigen levels (12·10%±6·08 of standard; 2 P <0·05) and non-significantly lower factor VII coagulant activity (8·24%±4·99 of standard) and fibrinogen concentrations (0·10±0·08 g.l−1) were observed. In contrast, plasminogen activator inhibitor activity was significantly higher (2·62±1·03 IU; 2 P <0·01) among patients allocated simvastatin. No significant differences were seen in the other haemostatic factors studied (e.g. prothrombin fragment 1·2, factor XII and C$$$ inhibitor). Total free fatty acid concentration was marginally significantly reduced (2 P =0·02) with simvastatin, but none of the reductions in individual free fatty acids was significant. Lipoprotein fractions were only measured among patients allocated 40 mg daily simvastatin or placebo. Compared with placebo, simvastatin produced significant decreases not only in LDL cholesterol (1·74±0·15 mmol.1−1; 2 P <0·0001) but also in VLDL cholesterol (0·28±0·08 mmol.1−1; 2 P <0·001) and IDL cholesterol (0·17±0·03 mmol.1−1; 2 P <0·0001). There were also lower triglyceride levels associated with LDL (0·07±0·01 mmol.1−1; 2 P <0·0001), IDL (0·03±0·01 mmol.1−1; 2 P <0·01) and VLDL (0·27±0·14; 2 P =0·05). The effects of simvastatin on haemostatic variables appear to be far less marked than its lipid effects. Given the associations of haemostatic factors with coronary heart disease incidence, larger randomized comparisons of the HMG-CoA re1ductase inhibitors (and of the newer fibrates, which may produce greater effects) are needed to provide more reliable estimates of the extent to which they influence these variables.

75 citations


Journal ArticleDOI
TL;DR: At the commencement of UKALL XI, a national MRC trial for childhood lymphoblastic leukaemia (ALL), the therapy included a bolus of daunorubicin (DR) on the first 2 d of the protocol, which was subsequently withdrawn because of concern about long‐term cardiotoxicity.
Abstract: At the commencement of UKALL XI, a national MRC trial for childhood lymphoblastic leukaemia (ALL), the therapy included a bolus of daunorubicin (DR) on the first 2 d of the protocol. This component of treatment was subsequently withdrawn because of concern about long-term cardiotoxicity. All children both before and after this change of policy had their marrow status at the end of the first week assessed by central review as part of the trial to examine the clinical importance of the rate of disease clearance. This also afforded an opportunity to observe the effect of DR on gross residual disease at an early stage of therapy. 1419 children were studied: 342 received DR (‘recipients’), 1077 did not. 44% of the recipients completely cleared their marrow of blast cells after 8 d compared with 13% of the non-recipients (χ2=158.2, P 80% blasts) was less impressive but there was still a difference in favour of DR recipients (DR 9%, no DR 15%; χ2=7.7, P=0.006). The rate of disease clearance correlated with disease-free survival for both recipients and non-recipients, but there was no significant difference in outcome when comparing the two groups with each other, either in terms of disease-free or relapse-free survival. DR accelerated the rate of blast cell disappearance from the marrow but the difference this made to disease free survival is small or non-existent. It appears to be the relative speed of response to a given therapeutic regimen that is prognostically important rather than the absolute rate of response when comparing one treatment with another.

39 citations


Journal ArticleDOI
TL;DR: Moderate alcohol consumption was associated with a reduction in mortality from vascular disease and a prospective study of mortality in relation to the consumption of alcohol in British doctors found that the apparently protective effect was likely to be partly or wholly real.
Abstract: Alcohol and coronary heart disease reduction among British doctors: confounding or causality? In the absence of experimental evidence, the interpretation of observed associations may be difficult unless they are exceptionally strong. There is no simple rule for distinguishing between associations of moderate strength that are partly or wholly causal and those that are entirely due to confounding between the factor under study and some other factor that is actually a cause of the disease. All importantly relevant evidence has to be taken into account, including the biological plausibility of causality. Several epidemiological studies have found an inverse association between the consumption of alcohol and coronary heart disease, and many authors have concluded that the most plausible explanation is that alcohol can be somewhat protective. Some, however , remain unconvinced. Shaper' 11 , for example, believes that the inverse association may well arise just because the non-drinking group is 'particularly predisposed to ill-health in all forms, and for several reasons, most particularly predisposed to coronary heart disease'. One widely discussed possibility is that the non-drinking group includes a substantial proportion of ex-drinkers who have given up alcohol because they already had heart disease, but the inverse relationship holds even after ex-drinkers have been excluded' 2 \" 41 and it also holds among men and women with no self-reported history of coronary heart disease in the past' 3 ' 5 \" 81. The other possible non-causal explanation for the observed inverse association involves confounding , lifelong abstainers being at relatively high risk because of some personal characteristics that affect the risk of the disease (other than the effects of their abstinence, or their past history of coronary disease). In our 1978-91 prospective study of mortality in relation to the consumption of alcohol in British doctors' 6 ' we, like many others, found that moderate alcohol consumption was associated with a reduction in mortality from vascular disease (Fig. 1) and concluded that the apparently protective effect was likely to be partly or wholly real. Shaper' 91 , however, has t I 0 21 42 63 Units (U.K.) of alcohol per week in 1978 questionnaire Figure 1 Trend in mortality from vascular disease (is-chaemic heart disease and stroke and residual vascular; ICD 9th revision 401-459) with consumption of alcohol (U.K. units per week) in British doctors 1978-1991. Floating absolute risk and 95% confidence interval, standardized for exact age and smoking. proposed that the lower …

31 citations


Journal ArticleDOI
TL;DR: This paper illustrates how collaboration in which those responsible for the trials supply data on each randomized patient for an individual patient data meta-analysis can help to achieve the aim of using complete data in a systematic review.
Abstract: Systematic reviews of randomized controlled trials often provide the most reliable information on which to base treatment policy. However, to be reliable, such reviews need to contain a high proportion of all the relevant randomized evidence. This relates both to the need to find all trials and the need to analyse data on all participants. One way to achieve this is through a collaboration in which those responsible for the trials supply data on each randomized patient for an individual patient data meta-analysis. However, such projects require more time and resources than more conventional reviews and are still rare. This paper illustrates how they can help to achieve the aim of using complete data in a systematic review.


Journal ArticleDOI
TL;DR: Future trials need to adopt simple design, streamlined data collection, and use of the "uncertainty principle' to guide eligibility in order to detect any moderate improvements in major outcomes that may await discovery.
Abstract: The reliable detection of moderate differences in major health outcomes that arise as a result of treatment requires large-scale randomized evidence (and the appropriate interpretation of this evidence once it has been generated). This may take the form of a single mega-trial or, exceptionally, a meta-analysis of many smaller randomized trials may provide worthwhile information. Small or non-randomized studies cannot generally be trusted to distinguish reliably between a moderate benefit, a moderate hazard, and a negligible difference in major outcomes. Simple design, streamlined data collection, and use of the ‘uncertainty principle’ to guide eligibility would all encourage the recruitment of larger samples in randomized trials. Future trials need to adopt these methods in order to detect any moderate improvements in major outcomes that may await discovery.

Journal ArticleDOI
TL;DR: The size of benefit conferred by continuing interferon α in patients who show no cytogenetic response, the best dose to use, and whether it should be given in combination with chemotherapy all remain uncertain at present.
Abstract: Interferon α is effective in the treatment of chronic myeloid leukaemia in terms of disease control. However, it is an expensive treatment compared with conventional chemotherapy and is not without side-effects. Examination of all the available randomized evidence demonstrates an absolute improvement in survival at 5 years of 15%±6% compared with conventional chemotherapy. There is no clear evidence that this benefit is different in any particular subgroup of patients. The size of benefit conferred by continuing interferon α in patients who show no cytogenetic response, the best dose to use, and whether it should be given in combination with chemotherapy all remain uncertain at present.

Journal ArticleDOI
04 Sep 1997-Nature
TL;DR: Weight is lent to this theory by two studies that link coronary heart disease to the bacterium Chlamydia pneumoniae, and the implications of these findings are discussed.
Abstract: A few weeks ago,Nature reported the sequence of Helicobacter pylori, which is present in up to one in three people and causes peptic ulcers. But many other chronic diseases or cancers are also thought to be caused by infectious agents. Weight is now lent to this theory by two studies that link coronary heart disease to the bacterium Chlamydia pneumoniae, and the implications of these findings are discussed.

Journal ArticleDOI