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R Peto

Publications and source records attributed to R Peto.

At least 19 recordsLinked to original sources
PubMed2005

Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials.

BACKGROUND: In early breast cancer, variations in local treatment that substantially affect the risk of locoregional recurrence could also affect long-term breast cancer mortality. To examine this relationship, collaborative meta-analyses were undertaken, based on individual patient data, of the relevant randomised trials that began by 1995. METHODS: Information was available on 42,000 women in 78 randomised treatment comparisons (radiotherapy vs no radiotherapy, 23,500; more vs less surgery, 9300; more surgery vs radiotherapy, 9300). 24 types of local treatment comparison were identified. To help relate the effect on local (ie, locoregional) recurrence to that on breast cancer mortality, these were grouped according to whether or not the 5-year local recurrence risk exceeded 10% (<10%, 17,000 women; >10%, 25,000 women). FINDINGS: About three-quarters of the eventual local recurrence risk occurred during the first 5 years. In the comparisons that involved little (<10%) difference in 5-year local recurrence risk there was little difference in 15-year breast cancer mortality. Among the 25,000 women in the comparisons that involved substantial (>10%) differences, however, 5-year local recurrence risks were 7% active versus 26% control (absolute reduction 19%), and 15-year breast cancer mortality risks were 44.6% versus 49.5% (absolute reduction 5.0%, SE 0.8, 2p<0.00001). These 25,000 women included 7300 with breast-conserving surgery (BCS) in trials of radiotherapy (generally just to the conserved breast), with 5-year local recurrence risks (mainly in the conserved breast, as most had axillary clearance and node-negative disease) 7% versus 26% (reduction 19%), and 15-year breast cancer mortality risks 30.5% versus 35.9% (reduction 5.4%, SE 1.7, 2p=0.0002; overall mortality reduction 5.3%, SE 1.8, 2p=0.005). They also included 8500 with mastectomy, axillary clearance, and node-positive disease in trials of radiotherapy (generally to the chest wall and regional lymph nodes), with similar absolute gains from radiotherapy; 5-year local recurrence risks (mainly at these sites) 6% versus 23% (reduction 17%), and 15-year breast cancer mortality risks 54.7% versus 60.1% (reduction 5.4%, SE 1.3, 2p=0.0002; overall mortality reduction 4.4%, SE 1.2, 2p=0.0009). Radiotherapy produced similar proportional reductions in local recurrence in all women (irrespective of age or tumour characteristics) and in all major trials of radiotherapy versus not (recent or older; with or without systemic therapy), so large absolute reductions in local recurrence were seen only if the control risk was large. To help assess the life-threatening side-effects of radiotherapy, the trials of radiotherapy versus not were combined with those of radiotherapy versus more surgery. There was, at least with some of the older radiotherapy regimens, a significant excess incidence of contralateral breast cancer (rate ratio 1.18, SE 0.06, 2p=0.002) and a significant excess of non-breast-cancer mortality in irradiated women (rate ratio 1.12, SE 0.04, 2p=0.001). Both were slight during the first 5 years, but continued after year 15. The excess mortality was mainly from heart disease (rate ratio 1.27, SE 0.07, 2p=0.0001) and lung cancer (rate ratio 1.78, SE 0.22, 2p=0.0004). INTERPRETATION: In these trials, avoidance of a local recurrence in the conserved breast after BCS and avoidance of a local recurrence elsewhere (eg, the chest wall or regional nodes) after mastectomy were of comparable relevance to 15-year breast cancer mortality. Differences in local treatment that substantially affect local recurrence rates would, in the hypothetical absence of any other causes of death, avoid about one breast cancer death over the next 15 years for every four local recurrences avoided, and should reduce 15-year overall mortality.

Aged↗
PubMed2005

Addition of clopidogrel to aspirin in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial.

BACKGROUND: Despite improvements in the emergency treatment of myocardial infarction (MI), early mortality and morbidity remain high. The antiplatelet agent clopidogrel adds to the benefit of aspirin in acute coronary syndromes without ST-segment elevation, but its effects in patients with ST-elevation MI were unclear. METHODS: 45,852 patients admitted to 1250 hospitals within 24 h of suspected acute MI onset were randomly allocated clopidogrel 75 mg daily (n=22,961) or matching placebo (n=22,891) in addition to aspirin 162 mg daily. 93% had ST-segment elevation or bundle branch block, and 7% had ST-segment depression. Treatment was to continue until discharge or up to 4 weeks in hospital (mean 15 days in survivors) and 93% of patients completed it. The two prespecified co-primary outcomes were: (1) the composite of death, reinfarction, or stroke; and (2) death from any cause during the scheduled treatment period. Comparisons were by intention to treat, and used the log-rank method. This trial is registered with ClinicalTrials.gov, number NCT00222573. FINDINGS: Allocation to clopidogrel produced a highly significant 9% (95% CI 3-14) proportional reduction in death, reinfarction, or stroke (2121 [9.2%] clopidogrel vs 2310 [10.1%] placebo; p=0.002), corresponding to nine (SE 3) fewer events per 1000 patients treated for about 2 weeks. There was also a significant 7% (1-13) proportional reduction in any death (1726 [7.5%] vs 1845 [8.1%]; p=0.03). These effects on death, reinfarction, and stroke seemed consistent across a wide range of patients and independent of other treatments being used. Considering all fatal, transfused, or cerebral bleeds together, no significant excess risk was noted with clopidogrel, either overall (134 [0.58%] vs 125 [0.55%]; p=0.59), or in patients aged older than 70 years or in those given fibrinolytic therapy. INTERPRETATION: In a wide range of patients with acute MI, adding clopidogrel 75 mg daily to aspirin and other standard treatments (such as fibrinolytic therapy) safely reduces mortality and major vascular events in hospital, and should be considered routinely.

Aged↗
PubMed2005

Early intravenous then oral metoprolol in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial.

BACKGROUND: Despite previous randomised trials of early beta-blocker therapy in the emergency treatment of myocardial infarction (MI), uncertainty has persisted about the value of adding it to current standard interventions (eg, aspirin and fibrinolytic therapy), and the balance of potential benefits and hazards is still unclear in high-risk patients. METHODS: 45,852 patients admitted to 1250 hospitals within 24 h of suspected acute MI onset were randomly allocated metoprolol (up to 15 mg intravenous then 200 mg oral daily; n=22,929) or matching placebo (n=22,923). 93% had ST-segment elevation or bundle branch block, and 7% had ST-segment depression. Treatment was to continue until discharge or up to 4 weeks in hospital (mean 15 days in survivors) and 89% completed it. The two prespecified co-primary outcomes were: (1) composite of death, reinfarction, or cardiac arrest; and (2) death from any cause during the scheduled treatment period. Comparisons were by intention to treat, and used the log-rank method. This study is registered with ClinicalTrials.gov, number NCT 00222573. FINDINGS: Neither of the co-primary outcomes was significantly reduced by allocation to metoprolol. For death, reinfarction, or cardiac arrest, 2166 (9.4%) patients allocated metoprolol had at least one such event compared with 2261 (9.9%) allocated placebo (odds ratio [OR] 0.96, 95% CI 0.90-1.01; p=0.1). For death alone, there were 1774 (7.7%) deaths in the metoprolol group versus 1797 (7.8%) in the placebo group (OR 0.99, 0.92-1.05; p=0.69). Allocation to metoprolol was associated with five fewer people having reinfarction (464 [2.0%] metoprolol vs 568 [2.5%] placebo; OR 0.82, 0.72-0.92; p=0.001) and five fewer having ventricular fibrillation (581 [2.5%] vs 698 [3.0%]; OR 0.83, 0.75-0.93; p=0.001) per 1000 treated. Overall, these reductions were counterbalanced by 11 more per 1000 developing cardiogenic shock (1141 [5.0%] vs 885 [3.9%]; OR 1.30, 1.19-1.41; p<0.00001). This excess of cardiogenic shock was mainly during days 0-1 after admission, whereas the reductions in reinfarction and ventricular fibrillation emerged more gradually. Consequently, the overall effect on death, reinfarction, arrest, or shock was significantly adverse during days 0-1 and significantly beneficial thereafter. There was substantial net hazard in haemodynamically unstable patients, and moderate net benefit in those who were relatively stable (particularly after days 0-1). INTERPRETATION: The use of early beta-blocker therapy in acute MI reduces the risks of reinfarction and ventricular fibrillation, but increases the risk of cardiogenic shock, especially during the first day or so after admission. Consequently, it might generally be prudent to consider starting beta-blocker therapy in hospital only when the haemodynamic condition after MI has stabilised.

Administration, Oral↗
PubMed2005

Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins.

BACKGROUND: Results of previous randomised trials have shown that interventions that lower LDL cholesterol concentrations can significantly reduce the incidence of coronary heart disease (CHD) and other major vascular events in a wide range of individuals. But each separate trial has limited power to assess particular outcomes or particular categories of participant. METHODS: A prospective meta-analysis of data from 90,056 individuals in 14 randomised trials of statins was done. Weighted estimates were obtained of effects on different clinical outcomes per 1.0 mmol/L reduction in LDL cholesterol. FINDINGS: During a mean of 5 years, there were 8186 deaths, 14,348 individuals had major vascular events, and 5103 developed cancer. Mean LDL cholesterol differences at 1 year ranged from 0.35 mmol/L to 1.77 mmol/L (mean 1.09) in these trials. There was a 12% proportional reduction in all-cause mortality per mmol/L reduction in LDL cholesterol (rate ratio [RR] 0.88, 95% CI 0.84-0.91; p<0.0001). This reflected a 19% reduction in coronary mortality (0.81, 0.76-0.85; p<0.0001), and non-significant reductions in non-coronary vascular mortality (0.93, 0.83-1.03; p=0.2) and non-vascular mortality (0.95, 0.90-1.01; p=0.1). There were corresponding reductions in myocardial infarction or coronary death (0.77, 0.74-0.80; p<0.0001), in the need for coronary revascularisation (0.76, 0.73-0.80; p<0.0001), in fatal or non-fatal stroke (0.83, 0.78-0.88; p<0.0001), and, combining these, of 21% in any such major vascular event (0.79, 0.77-0.81; p<0.0001). The proportional reduction in major vascular events differed significantly (p<0.0001) according to the absolute reduction in LDL cholesterol achieved, but not otherwise. These benefits were significant within the first year, but were greater in subsequent years. Taking all years together, the overall reduction of about one fifth per mmol/L LDL cholesterol reduction translated into 48 (95% CI 39-57) fewer participants having major vascular events per 1000 among those with pre-existing CHD at baseline, compared with 25 (19-31) per 1000 among participants with no such history. There was no evidence that statins increased the incidence of cancer overall (1.00, 0.95-1.06; p=0.9) or at any particular site. INTERPRETATION: Statin therapy can safely reduce the 5-year incidence of major coronary events, coronary revascularisation, and stroke by about one fifth per mmol/L reduction in LDL cholesterol, largely irrespective of the initial lipid profile or other presenting characteristics. The absolute benefit relates chiefly to an individual's absolute risk of such events and to the absolute reduction in LDL cholesterol achieved. These findings reinforce the need to consider prolonged statin treatment with substantial LDL cholesterol reductions in all patients at high risk of any type of major vascular event.

Cause of Death↗
PubMed2005

Mortality from cancer in relation to smoking: 50 years observations on British doctors.

A total of 34,439 male British doctors, who reported their smoking habits in November 1951, were followed, with periodic up date of changes in their habits, until death, emigration, censoring. or November 2001. Information was obtained about their mortality from 28 of the 30 types of cancer in men reviewed by the International Agency for Research on Cancer (no death was recorded from the other two). In all, 11 of the 13 types in men that the Agency classed as liable to be caused by smoking were significantly related to smoking and the findings for the other two, which caused only few deaths, suggested they might be. Of the 13 types in men for which the Agency found only sparse or inconsistent data and for which we had data, only two appeared to be possibly related (one positively, one negatively), and the 638 deaths for the summed group were clearly unrelated to smoking. Of the two types for which the Agency thought that the relationship with smoking might be due to bias or confounding, the findings for one (prostate cancer) tended to support the belief that smoking was unrelated, and those for the other (colorectal cancer) showed a weak relationship with smoking, which (in a small subset) could not be attributed to confounding with the consumption of alcohol.

Alcohol Drinking↗
PubMed2004

Prevention of disabling and fatal strokes by successful carotid endarterectomy in patients without recent neurological symptoms: randomised controlled trial.

BACKGROUND: Among patients with substantial carotid artery narrowing but no recent neurological symptom (stroke or transient ischaemia), the balance of surgical risks and long-term benefits from carotid endarterectomy (CEA) was unclear. METHODS: During 1993-2003, 3120 asymptomatic patients with substantial carotid narrowing were randomised equally between immediate CEA (half got CEA by 1 month, 88% by 1 year) and indefinite deferral of any CEA (only 4% per year got CEA) and were followed for up to 5 years (mean 3.4 years). Kaplan-Meier analyses of 5-year risks are by allocated treatment. FINDINGS: The risk of stroke or death within 30 days of CEA was 3.1% (95% CI 2.3-4.1). Comparing all patients allocated immediate CEA versus all allocated deferral, but excluding such perioperative events, the 5-year stroke risks were 3.8% versus 11% (gain 7.2% [95% CI 5.0-9.4], p<0.0001). This gain chiefly involved carotid territory ischaemic strokes (2.7% vs 9.5%; gain 6.8% [4.8-8.8], p<0.0001), of which half were disabling or fatal (1.6% vs 5.3%; gain 3.7% [2.1-5.2], p<0.0001), as were half the perioperative strokes. Combining the perioperative events and the non-perioperative strokes, net 5-year risks were 6.4% versus 11.8% for all strokes (net gain 5.4% [3.0-7.8], p<0.0001), 3.5% versus 6.1% for fatal or disabling strokes (net gain 2.5% [0.8-4.3], p=0.004), and 2.1% versus 4.2% just for fatal strokes (net gain 2.1% [0.6-3.6], p=0.006). Subgroup-specific analyses found no significant heterogeneity in the perioperative hazards or (apart from the importance of cholesterol) in the long-term postoperative benefits. These benefits were separately significant for males and females; for those with about 70%, 80%, and 90% carotid artery narrowing on ultrasound; and for those younger than 65 and 65-74 years of age (though not for older patients, half of whom die within 5 years from unrelated causes). Full compliance with allocation to immediate CEA or deferral would, in expectation, have produced slightly bigger differences in the numbers operated on, and hence in the net 5-year benefits. The 10-year benefits are not yet known. INTERPRETATION: In asymptomatic patients younger than 75 years of age with carotid diameter reduction about 70% or more on ultrasound (many of whom were on aspirin, antihypertensive, and, in recent years, statin therapy), immediate CEA halved the net 5-year stroke risk from about 12% to about 6% (including the 3% perioperative hazard). Half this 5-year benefit involved disabling or fatal strokes. But, outside trials, inappropriate selection of patients or poor surgery could obviate such benefits.

Aged↗
PubMed2004

Tobacco attributable deaths in South Africa.

BACKGROUND: In mid 1998, a question "Was the deceased a smoker five years ago?" was introduced on the newly revised South African death notification form. DESIGN: A total of 16,230 new death notification forms from 1998 have been coded, and comparison of the prevalence of smoking among those who died of different causes was used to estimate, by case-control comparisons, tobacco attributed mortality in South Africa. Cases comprised deaths from causes known (from other studies) to be causally associated with smoking, and controls comprised deaths from medical conditions expected to be unrelated to smoking. Those who died from external causes, and from diseases strongly related to alcohol consumption, were excluded. SUBJECTS: Reports were available from 5340 deceased adults (age 25+), whose smoking status was given by a family member. RESULTS: Significantly increased risks were found for deaths from tuberculosis (odds ratio (OR) 1.61, 95% confidence interval (CI) 1.23 to 2.11), chronic obstructive pulmonary disease (COPD) (OR 2.5, 95% CI 1.9 to 3.4), lung cancer (OR 4.8, 95% CI 2.9 to 8.0), other upper aerodigestive cancer (OR 3.0, 95% CI 1.9 to 4.9) and ischaemic heart disease (OR 1.7, 95% CI 1.2 to 2.3). CONCLUSION: If smokers had the same death rate as non-smokers, 58% of lung cancer deaths, 37% of COPD deaths, 20% of tuberculosis deaths, and 23% of vascular deaths would have been avoided. About 8% of all adult deaths in South Africa (more than 20 000 deaths a year) were caused by smoking.

Adult↗
PubMed2003

Treatment of cutaneous leishmaniasis with aminosidine (paromomycin) ointment: double-blind, randomized trial in the Islamic Republic of Iran.

OBJECTIVE: To compare the parasitological and clinical efficacy of four weeks versus two weeks of treatment with aminosidine (paromomycin) ointment in patients with cutaneous leishmaniasis caused by Leishmania major in the Islamic Republic of Iran. METHODS: Double-blind, randomized trial of four weeks of aminosidine ointment (n = 108) vs two weeks of aminosidine ointment and two weeks of placebo (n = 108). Patients were assessed on days 15, 29, 45, and 105 for clinical cures and clinical and parasitological cures. FINDINGS: Four weeks' treatment gave significantly better cure rates than two weeks' treatment: on day 29, there were 80/108 (74%) vs 64/108 (59%) clinical cures (P = 0.05) and 47 (44%) vs 26 (24%) clinical and parasitological cures (P = 0.005). By day 45, fewer patients who received four weeks' treatment had required rescue treatment with antimonials than those who received two weeks' treatment: 20 (19%) vs 36 (33%) (P = 0.02). On day 105, the results still favoured those who had been allocated four weeks of active treatment, but the differences were no longer as clearly significant. No side-effects were observed or reported. CONCLUSION: Approximately two-thirds of patients given ointment for four weeks were cured clinically. Although about half of those cured might have recovered spontaneously even without treatment, four weeks of aminosidine ointment could become the first-line treatment for uncomplicated cutaneous leishmaniasis due to L. major, with antimonials needed in only the one-third of patients not cured by the end of treatment with aminosidine. This would considerably reduce the costs and side-effects associated with antimonial drugs.

Antiprotozoal Agents↗
PubMed2003

CNS-directed therapy for childhood acute lymphoblastic leukemia: Childhood ALL Collaborative Group overview of 43 randomized trials.

PURPOSE: A collaborative meta-analysis was performed to clarify the relative effects on relapse and survival of different types of therapies directed at the CNS in childhood acute lymphoblastic leukemia. MATERIALS AND METHODS: Data were sought for each individual patient in all trials started in or before 1993 that included unconfounded randomized comparisons of such treatments. Log-rank survival analyses were performed for each trial, and overall results for groups of trials addressing similar questions were obtained from the totals of the observed minus expected number of events and their variances. RESULTS: Radiotherapy and long-term intrathecal therapy gave similar outcomes, with no significant difference in event-free survival despite random assignment of treatment to 2,848 patients, 1,001 of whom suffered relapse or death. Intravenous methotrexate reduced non-CNS rather than CNS relapses, and hence, the addition of intravenous methotrexate to a treatment regimen including radiotherapy or long-term intrathecal therapy improved event-free survival, with a 17% reduction in the event rate (95% confidence interval, 6% to 27%; P =.003). The event-free survival at 10 years in these trials was 61.9% without intravenous methotrexate and 68.1% with intravenous methotrexate. There was no significant difference in survival (14% death rate reduction; P =.09). There were insufficient randomly assigned patients to adequately address other questions, such as effect of different doses. No evidence was found of differences, between trials or between subgroups of different types of patients, in the relative effects of treatment. CONCLUSION: Radiotherapy can be replaced by long-term intrathecal therapy. Intravenous methotrexate gives some additional benefit by reducing non-CNS relapses.

Antimetabolites, Antineoplastic↗
PubMed2002

Underestimation of the importance of blood pressure and cholesterol for coronary heart disease mortality in old age.

AIMS: To take appropriate account of duration of follow-up in estimating age-specific associations of 'usual' blood pressure and cholesterol with death from coronary heart disease. METHODS AND RESULTS: Blood pressure and cholesterol were measured in 18 841 men at entry to the Whitehall study, and coronary heart disease mortality was recorded during a 26-year period. Biennial re-measurements of these risk factors in the Framingham study were used to obtain period-specific corrections for 'regression dilution'. For coronary heart disease deaths at ages 40-64, 65-74 and 75+ years in the Whitehall study, the mean times since baseline were 9, 15, and 21 years, respectively. In uncorrected analyses of coronary heart disease risk in each age range, a 10 mmHg lower systolic blood pressure at baseline was associated with proportional risk reductions of only 19%, 14% and 10%, respectively (P<0.001 for trend with age). After period-specific correction for regression dilution, a 10 mmHg lower usual systolic blood pressure about 5 years before coronary heart disease death was associated with risk reductions of 25%, 23% and 21%, respectively (trend P=0.1). Similarly, a 1 mmol . l(-1)lower blood cholesterol was associated with proportional reductions in coronary heart disease risk of 21%, 17% and 11% (trend P<0.001) in uncorrected analyses, by contrast with proportional reductions of 27%, 26% and 21% (trend P=0.5) after period-specific correction. CONCLUSIONS: After making appropriate allowance for the longer interval between baseline measurements and death at older ages, reductions in the risk of coronary heart disease death associated with differences in usual levels of blood pressure or cholesterol at some particular fixed time prior to death were about as great in old age as in middle age.

Adult↗
PubMed2001

Mortality and smoking in Hong Kong: case-control study of all adult deaths in 1998.

OBJECTIVE: To assess the mortality currently associated with smoking in Hong Kong, and, since cigarette consumption reached its peak 20 years earlier in Hong Kong than in mainland China, to predict mortality in China 20 years hence. DESIGN: Case-control study. Past smoking habits of all Chinese adults in Hong Kong who died in 1998 (cases) were sought from those registering the death. SETTING: All the death registries in Hong Kong. PARTICIPANTS: 27 507 dead cases (81% of all registered deaths) and 13 054 live controls aged >/=35 years. MAIN OUTCOME MEASURES: Mortality from all causes and from specific causes. RESULTS: In men aged 35-69 the adjusted risk ratios (and 95% confidence intervals) comparing smokers with non-smokers were 1.92 (1.70 to 2.16) for all deaths, 2.22 (1.94 to 2.55) for neoplastic deaths, 2.60 (2.10 to 3.21) for respiratory deaths (including tuberculosis, risk ratio 2.54), and 1.68 (1.43 to 1.97) for vascular deaths (each P<0.0001). In women aged 35-69 the corresponding risk ratios were 1.62 (1.40 to 1.88) for all deaths, 1.60 (1.33 to 1.93) for neoplastic deaths, 3.13 (2.21 to 4.44) for respiratory deaths, and 1.55 (1.20 to 1.99) for vascular deaths (each P<0.001). If these associations with smoking are largely or wholly causal then, among all registered deaths at ages 35-69 in 1998, tobacco caused about 33% (2534/7588) of all male deaths and 5% (169/3341) of all female deaths (hence 25% of all deaths at these ages). At older ages tobacco seemed to be the cause of 15% (3017/20 420) of all deaths. CONCLUSIONS: Among middle aged men the proportion of deaths caused by smoking is more than twice as big in Hong Kong now (33%) as in mainland China 10 years earlier. This supports predictions of a large increase in tobacco attributable mortality in China as a whole.

Adult↗
PubMed2001

A prospective study of Helicobacter pylori seropositivity and the risk for future myocardial infarction among socioeconomically similar U.S. men.

BACKGROUND: The role of Helicobacter pylori as a determinant of cardiovascular disease is controversial. OBJECTIVE: To determine whether previous exposure to H. pylori is associated with an increased risk for myocardial infarction. DESIGN: Prospective case-control study. SETTING: Physicians' Health Study. PARTICIPANTS: Initially healthy U.S. men. MEASUREMENTS: Titers of IgG antibody against H. pylori and several inflammatory markers were measured in baseline blood samples obtained from 445 men who subsequently had a myocardial infarction (case-patients) and 445 men matched for age and smoking status who remained free of vascular disease (controls) during a mean follow-up of 8.9 years. RESULTS: Baseline seropositivity was similar among case-patients and controls (43.4% vs. 44.3%; rate ratio, 0.96 [95% CI, 0.7 to 1.3]). Minimal evidence of association was found between magnitude of seropositivity and subsequent risk and between seropositivity and levels of the inflammatory biomarkers. CONCLUSION: In a socioeconomically homogeneous population, we found limited evidence of association between H. pylori exposure and risk for future myocardial infarction.

Biomarkers↗