Individually, randomised trials have not shown conclusively whether adjuvant chemotherapy benefits adult patients with localised resectable soft-tissue sarcoma.

There have been 13 randomised controlled trials of prophylactic amiodarone in patients with recent myocardial infarction (MI) or congestive heart failure (CHF). None of these was powered to detect a mortality reduction of about 20%. We undertook a meta-analysis, based on data from individual patients, to provide a more sensitive and accurate assessment of the benefits and risks of prophylactic amiodarone.

Homeopathy seems scientifically implausible, but has widespread use. We aimed to assess whether the clinical effect reported in randomised controlled trials of homeopathic remedies is equivalent to that reported for placebo.

Recent trials of thrombolytic therapy in acute ischaemic stroke have given apparently conflicting results. Only one trial, the National Institute of Neurological Disorders and Stroke trial of tissue plasminogen activator (tPA), suggested that thrombolysis was definitely beneficial. To make sense of these results, we have done a systematic review of all available randomised trials of thrombolysis in acute ischaemic stroke.

Among women with early breast cancer, the effects of ovarian ablation on recurrence and death have been assessed by several randomised trials that now have long follow-up. In this report, the Early Breast Cancer Trialists' Collaborative Group present their third 5-yearly systematic overview (meta-analysis), now with 15 years' follow-up.

Respiratory rehabilitation is increasingly recognised as an important part of the management of patients with chronic obstructive pulmonary disease (COPD). The widespread application of such programmes should be preceded by evidence of directly attributable improvements in function. We assessed the effect of respiratory rehabilitation on exercise capacity and health-related quality of life (HRQL) in patients with COPD.

There have been no studies showing that participation in programmes which provide legal access to drug-injection equipment leads to individual-level protection against incident HIV infection. We have compared HIV incidence among injecting drug users participating in syringe-exchange programmes in New York City with that among non-participants.

There is conclusive evidence from clinical trials that reduction of mortality by fibrinolytic therapy in acute myocardial infarction is related to the time elapsing between onset of symptoms and commencement of treatment. However, the exact pattern of this relation continues to be debated. This paper discusses whether or not appreciable additional gain can be achieved with very early treatment.

The effects on long-term outcome in childhood acute lymphoblastic leukaemia (ALL) of the duration and the intensity of maintenance chemotherapy need to be assessed reliably. With this objective the Childhood ALL Collaborative Group coordinated a worldwide overview of all randomised trials that began before 1987.

BACKGROUND The Collaborative Group on Hormonal Factors in Breast Cancer has brought together and reanalysed the worldwide epidemiological evidence on the relation between breast cancer risk and use of hormonal contraceptives. METHODS Individual data on 53 297 women with breast cancer and 100 239 women without breast cancer from 54 studies conducted in 25 countries were collected, checked, and analysed centrally. Estimates of the relative risk for breast cancer were obtained by a modification of the Mantel-Haenszel method. All analyses were stratified by study, age at diagnosis, parity, and, where appropriate, the age a woman was when her first child was born, and the age she was when her risk of conception ceased. FINDINGS The results provide strong evidence for two main conclusions. First, while women are taking combined oral contraceptives and in the 10 years after stopping there is a small increase in the relative risk of having breast cancer diagnosed (relative risk [95 percent CI] in current users 1.24 [1.15-1.33], 2p<0.00001; 1-4 years after stopping 1.16 [1.08-1.23], 2p=0.00001; 5-9 years after stopping 1.07 [1.02-1.13], 2p=0.009). Second, there is no significant excess risk of having breast cancer diagnosed 10 or more years after stopping use (relative risk 1.01 [0.96-1.05], NS). The cancers diagnosed in women who had used combined oral contraceptives were less advanced clinically than those diagnosed in women who had never used these contraceptives for ever-users compared with never-users, the relative risk for tumours that had spread beyond the breast compared with localised tumours was 0.88 (0.81-0.95; 2p=0.002). There was no pronounced variation in the results for recency of use between women with different background risks of breast cancer, including women from different countries and ethnic groups, women with different reproductive histories, and those with or without a family history of breast cancer. The studies included in this collaboration represent about 90 percent of the epidemiological information on the topic, and what is known about the other studies suggests that their omission has not materially affected the main conclusions. Other features of hormonal contraceptive use such as duration of use, age at first use, and the dose and type of hormone within the contraceptives had little additional effect on breast cancer risk, once recency of use had been taken into account. Women who began use before age 20 had higher relative risks of having breast cancer diagnosed while they were using combined oral contraceptives and in the 5 years after stopping than women who began use at older ages, but the higher relative risks apply at ages when breast cancer is rare and, for a given duration of use, earlier use does not result in more cancers being diagnosed than use beginning at older ages. Because breast cancer incidence rises steeply with age, the estimated excess number of cancers diagnosed in the period between starting use and 10 years after stopping increases with age at last use: for example, among 10 000 women from Europe or North America who used oral contraceptives from age 16 to 19, from age 20 to 24, and from age 25 to 29, respectively, the estimated excess number of cancers diagnosed up to 10 years after stopping use is 0.5 (95 percent CI 0.3-0.7), 1.5 (0.7-2.3), and 4.7 (2.7-6.7). Up to 20 years after cessation of use the difference between ever-users and never-users is not so much in the total number of cancers diagnosed, but in their clinical presentation, with the breast cancers diagnosed in ever-users being less advanced clinically than those diagnosed in never-users. The relation observed between breast cancer risk and hormone exposure is unusual, and it is not possible to infer from these data whether it is due to an earlier diagnosis of breast cancer in ever-users, the biological effects of hormonal contraceptives, or a combination of reasons...

Adjuvant tamoxifen for early breast cancer provides an improvement in relapse-free (RFS) and overall survival (OS), especially for older women. We carried out a meta-analysis to find out whether the benefit of adding chemotherapy to tamoxifen outweighs its costs in terms of toxic effects for postmenopausal patients.

A patient with severe angina will often be eligible for either angioplasty (PTCA) or bypass surgery (CABG). Results from eight published randomised trials have been combined in a collaborative meta-analysis of 3371 patients (1661 CABG, 1710 PTCA) with a mean follow-up of 2.7 years. The total deaths in the CABG and PTCA groups were 73 and 79, respectively, with a relative risk (RR) of 1.08 (95% CI 0.79-1.50). The combined endpoint of cardiac death and non-fatal myocardial infarction occurred in 169 PTCA patients and 154 CABG patients (RR 1.10 [0.89-1.37]). Amongst patients randomised to PTCA 17.8% required additional CABG within a year, while in subsequent years the need for additional CABG was around 2% per annum. The rate of additional non-randomised interventions (PTCA and/or CABG) in the first year of follow-up was 33.7% and 3.3% in patients randomised to PTCA and CABG, respectively. The prevalence of angina after one year was considerably higher in the PTCA group (RR 1.56 [1.30-1.88]) but at 3 years this difference had attenuated (RR 1.22 [0.99-1.54]). Overall there was substantial similarity in outcome across the trials. Separate analyses for the 732 single-vessel and 2639 multivessel disease patients were largely compatible, though the rates of mortality, additional intervention, and prevalent angina were slightly lower in single vessel disease. The combined evidence comparing PTCA with CABG shows no difference in prognosis between these two initial revascularisation strategies. However, the treatments differ markedly in the subsequent requirement for additional revascularisation procedures and in the relief of angina. These results will influence the choice of revascularisation procedure in future patients with angina.

The observation of an exponential increase in senile dementia prevalence with age has led to the conclusion that this disease may be inevitable in those who live long enough. The alternative view is that at very high ages the prevalence rate levels off. Studies conducted to date have not included sufficient numbers of very old people to resolve this difference of opinion. The question is important both to our understanding of the biological mechanisms involved and for public health planning. We have carried out a meta-analysis of nine epidemiological studies of senile dementia that used DSM III diagnostic criteria and that included samples of elderly people over age 80. The resulting curve was best described as a flattened S curve that fitted a modified logistic function rather than an exponential pattern. The rate of increase in senile dementia prevalence was found to fall in the age range 80-84, and at around the age of 95 prevalence was seen to level off to about 40%. It seems that senile dementia is better conceptualised as an "age-related" (ie, occurring within a specific age range) rather than as an "ageing-related" disorder (that is, caused by the ageing process itself). Very elderly survivors may be at diminishing risk of dementia and this has implications for public health policy.

A systematic overview, or meta-analysis, of the randomised evidence on maximum androgen blockade (MAB) in advanced prostate cancer identified 25 trials that compared conventional castration (surgical or medical) versus MAB (castration plus prolonged use of an antiandrogen such as flutamide, cyproterone acetate, or nilutamide). Individual patient data were obtained from 22 of the trials. Median follow-up was 40 months, during which 57% of patients died (3283/5710). Crude mortality rates were 58% for castration alone and 56% for MAB. Life-table estimates of the corresponding 5-year survival rates were 22.8% and 26.2%, representing a non-significant improvement of 3.5% (95% CI 0-7%). Logrank time-to-death analyses found no significant heterogeneity between trials (or between the effects of different types of MAB) and no significant evidence of additional benefit in an overview of all these MAB trial results (2p > 0.1). The currently available evidence from randomised trials does not show that MAB results in longer survival than conventional castration.

We tested, under independent conditions, the reproducibility of evidence from two previous trials that homoeopathy differs from placebo. The test model was again homoeopathic immunotherapy. 28 patients with allergic asthma, most of them sensitive to house-dust mite, were randomly allocated to receive either oral homoeopathic immunotherapy to their principal allergen or identical placebo. The test treatments were given as a complement to their unaltered conventional care. A daily visual analogue scale of overall symptom intensity was the outcome measure. A difference in visual analogue score in favour of homoeopathic immunotherapy appeared within one week of starting treatment and persisted for up to 8 weeks (p = 0.003). There were similar trends in respiratory function and bronchial reactivity tests. A meta-analysis of all three trials strengthened the evidence that homoeopathy does more than placebo (p = 0.0004). Is the reproducibility of evidence in favour of homoeopathy proof of its activity or proof of the clinical trial's capacity to produce false-positive results?