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Treatment with daily aspirin for 5 years or longer reduces subsequent risk of colorectal cancer. Several lines of evidence suggest that aspirin might also reduce risk of other cancers, particularly of the gastrointestinal tract, but proof in man is lacking. We studied deaths due to cancer during and after randomised trials of daily aspirin versus control done originally for prevention of vascular events. We used individual patient data from all randomised trials of daily aspirin versus no aspirin with mean duration of scheduled trial treatment of 4 years or longer to determine the effect of allocation to aspirin on risk of cancer death in relation to scheduled duration of trial treatment for gastrointestinal and non-gastrointestinal cancers. In three large UK trials, long-term post-trial follow-up of individual patients was obtained from death certificates and cancer registries. In eight eligible trials (25 570 patients, 674 cancer deaths), allocation to aspirin reduced death due to cancer (pooled odds ratio [OR] 0·79, 95% CI 0·68–0·92, p=0·003). On analysis of individual patient data, which were available from seven trials (23 535 patients, 657 cancer deaths), benefit was apparent only after 5 years' follow-up (all cancers, hazard ratio [HR] 0·66, 0·50–0·87; gastrointestinal cancers, 0·46, 0·27–0·77; both p=0·003). The 20-year risk of cancer death (1634 deaths in 12 659 patients in three trials) remained lower in the aspirin groups than in the control groups (all solid cancers, HR 0·80, 0·72–0·88, p<0·0001; gastrointestinal cancers, 0·65, 0·54–0·78, p<0·0001), and benefit increased (interaction p=0·01) with scheduled duration of trial treatment (≥7·5 years: all solid cancers, 0·69, 0·54–0·88, p=0·003; gastrointestinal cancers, 0·41, 0·26–0·66, p=0·0001). The latent period before an effect on deaths was about 5 years for oesophageal, pancreatic, brain, and lung cancer, but was more delayed for stomach, colorectal, and prostate cancer. For lung and oesophageal cancer, benefit was confined to adenocarcinomas, and the overall effect on 20-year risk of cancer death was greatest for adenocarcinomas (HR 0·66, 0·56–0·77, p<0·0001). Benefit was unrelated to aspirin dose (75 mg upwards), sex, or smoking, but increased with age—the absolute reduction in 20-year risk of cancer death reaching 7·08% (2·42–11·74) at age 65 years and older. Daily aspirin reduced deaths due to several common cancers during and after the trials. Benefit increased with duration of treatment and was consistent across the different study populations. These findings have implications for guidelines on use of aspirin and for understanding of carcinogenesis and its susceptibility to drug intervention. None.

High-dose aspirin (≥500 mg daily) reduces long-term incidence of colorectal cancer, but adverse effects might limit its potential for long-term prevention. The long-term effectiveness of lower doses (75–300 mg daily) is unknown. We assessed the effects of aspirin on incidence and mortality due to colorectal cancer in relation to dose, duration of treatment, and site of tumour. We followed up four randomised trials of aspirin versus control in primary (Thrombosis Prevention Trial, British Doctors Aspirin Trial) and secondary (Swedish Aspirin Low Dose Trial, UK-TIA Aspirin Trial) prevention of vascular events and one trial of different doses of aspirin (Dutch TIA Aspirin Trial) and established the effect of aspirin on risk of colorectal cancer over 20 years during and after the trials by analysis of pooled individual patient data. In the four trials of aspirin versus control (mean duration of scheduled treatment 6·0 years), 391 (2·8%) of 14 033 patients had colorectal cancer during a median follow-up of 18·3 years. Allocation to aspirin reduced the 20-year risk of colon cancer (incidence hazard ratio [HR] 0·76, 0·60–0·96, p=0·02; mortality HR 0·65, 0·48–0·88, p=0·005), but not rectal cancer (0·90, 0·63–1·30, p=0·58; 0·80, 0·50–1·28, p=0·35). Where subsite data were available, aspirin reduced risk of cancer of the proximal colon (0·45, 0·28–0·74, p=0·001; 0·34, 0·18–0·66, p=0·001), but not the distal colon (1·10, 0·73–1·64, p=0·66; 1·21, 0·66–2·24, p=0·54; for incidence difference p=0·04, for mortality difference p=0·01). However, benefit increased with scheduled duration of treatment, such that allocation to aspirin of 5 years or longer reduced risk of proximal colon cancer by about 70% (0·35, 0·20–0·63; 0·24, 0·11–0·52; both p<0·0001) and also reduced risk of rectal cancer (0·58, 0·36–0·92, p=0·02; 0·47, 0·26–0·87, p=0·01). There was no increase in benefit at doses of aspirin greater than 75 mg daily, with an absolute reduction of 1·76% (0·61–2·91; p=0·001) in 20-year risk of any fatal colorectal cancer after 5-years scheduled treatment with 75–300 mg daily. However, risk of fatal colorectal cancer was higher on 30 mg versus 283 mg daily on long-term follow-up of the Dutch TIA trial (odds ratio 2·02, 0·70–6·05, p=0·15). Aspirin taken for several years at doses of at least 75 mg daily reduced long-term incidence and mortality due to colorectal cancer. Benefit was greatest for cancers of the proximal colon, which are not otherwise prevented effectively by screening with sigmoidoscopy or colonoscopy. None.

Cerebral cavernous malformations (CCMs) are prone to bleeding but the risk of intracranial haemorrhage and focal neurological deficits, and the factors that might predict their occurrence, are unclear. We aimed to quantify these risks and investigate whether they are affected by sex and CCM location. We undertook a population-based study using multiple overlapping sources of case ascertainment (including a Scotland-wide collaboration of neurologists, neurosurgeons, stroke physicians, radiologists, and pathologists, as well as searches of registers of hospital discharges and death certificates) to identify definite CCM diagnoses first made in Scottish residents between 1999 and 2003, which study neuroradiologists independently validated. We used multiple sources of prospective follow-up both to identify outcome events (which were assessed by use of brain imaging, by investigators masked to potential predictive factors) and to assess adults' dependence. The primary outcome was a composite of intracranial haemorrhage or focal neurological deficits (not including epileptic seizure) that were definitely or possibly related to CCM. 139 adults had at least one definite CCM and 134 were alive at initial presentation. During 1177 person-years of follow-up (completeness 97%), for intracranial haemorrhage alone the 5-year risk of a first haemorrhage was lower than the risk of recurrent haemorrhage (2·4%, 95% CI 0·0–5·7 vs 29·5%, 4·1–55·0; p<0·0001). For the primary outcome, the 5-year risk of a first event was lower than the risk of recurrence (9·3%, 3·1–15·4 vs 42·4%, 26·8–58·0; p<0·0001). The annual risk of recurrence of the primary outcome declined from 19·8% (95% CI 6·1–33·4) in year 1 to 5·0% (0·0–14·8) in year 5 and was higher for women than men (p=0·01) but not for adults with brainstem CCMs versus CCMs in other locations (p=0·17). The risk of recurrent intracranial haemorrhage or focal neurological deficit from a CCM is greater than the risk of a first event, is greater for women than for men, and declines over 5 years. This information can be used in clinical practice, but further work is needed to quantify risks precisely in the long term and to understand why women are at greater risk of recurrence than men. UK Medical Research Council, Chief Scientist Office of the Scottish Government, and UK Stroke Association.

Sub-Saharan Africa is undergoing epidemiological transition. Stroke and other vascular diseases increasingly contribute to the burden of disease. There are no systematic reviews of stroke mortality, prevalence, incidence, and case fatality. We combined a thorough search and critical assessment of the published research. Stroke mortality is as high, perhaps higher, than in high-income regions and increases with age in sub-Saharan Africa as in high-income countries, but the absolute number of stroke deaths remains low. There are no adequate community-based stroke incidence studies. Hospital-based incidence is lower than in high-income regions, but higher in young people, possibly due to hospital admission bias. There are no community-based data on case fatality, but hospital-based case fatality is higher than elsewhere. The prevalence of stroke is lower than in high-income regions, but disabling stroke is as prevalent. As the region develops economically, the incidence of stroke and other vascular diseases will increase unless interventions are implemented. Only community-based incidence studies will accurately reveal the burden of stroke.

This review of the effectiveness of treatment for acute stroke and methods of secondary prevention shows that the highest priority for providers of a stroke service must be to establish a stroke unit and multidisciplinary team that delivers organised stroke care. Acute ischaemic stroke patients should be immediately started on aspirin 300 mg daily, and, if possible, many of them should be entered into further trials of thrombolysis and other promising treatments. After the acute phase, aspirin should be continued in a lower dose, 75 mg daily; smoking should be discouraged; high blood pressure treated initially with a diuretic; and fibrillating ischaemic stroke/transient ischaemic attack survivors anticoagulated long-term with warfarin or given aspirin if anticoagulation is not sensible. Statins are probably indicated in patients who already have symptomatic coronary heart disease. Adding dipyridamole to aspirin, substituting clopidogrel for aspirin, and carotid endarterectomy are all expensive interventions to prevent stroke, but if ways could be found to focus them on those patients at especially high risk, they would become more affordable.

The decision about whether to treat an unruptured brain arteriovenous malformation (AVM) depends on a comparison of the estimated lifetime risk of intracranial haemorrhage with the risks of interventional treatment. We aimed to test whether outcome differs between adults who had interventional AVM treatment and those who did not. All adults in Scotland who were first diagnosed with an unruptured AVM during 1999–2003 (n=114) entered our prospective, population-based study. We compared the baseline characteristics and 3-year outcome of adults who received interventional treatment for their AVM (n=63) with those who did not (n=51). At presentation, adults who were treated were younger (mean 40 vs 55 years of age, 95% CI for difference 9–20; p<0·0001), more likely to present with a seizure (odds ratio 2·4, 95% CI 1·1–5·0), and had fewer comorbidities (median 3 vs 4, p=0·03) than those who were not treated. Despite these baseline imbalances, treated and untreated groups did not differ in progression to Oxford Handicap Scale (OHS) scores of 2–6 (log-rank p=0·12) or 3–6 (log-rank p=0·98) in survival analyses. In a multivariable Cox proportional hazards analysis, the risk of poor outcome (OHS 2–6) was greater in patients who had interventional treatment than in those who did not (hazard ratio 2·5, 95% CI 1·1–6·0) and was greater in patients with a larger AVM nidus (hazard ratio 1·3, 95% CI 1·1–1·7). The treated and untreated groups did not differ in time to an OHS score of 2 or more that was sustained until the end of the third year of follow-up, or in the spectrum of dependence as measured by the OHS at 1, 2, and 3 years of follow-up. Greater AVM size and interventional treatment were associated with worse short-term functional outcome for unruptured AVMs, but the longer-term effects of intervention are unclear.

Clinicians often have to make treatment decisions based on the likelihood that an individual patient will benefit. In this article we consider the relevance of relative and absolute risk reductions, and draw attention to the importance of expressing the results of trials and subgroup analyses in terms of absolute risk. We describe the limitations of univariate subgroup analysis in situations in which there are several determinants of treatment effect, and review the potential for targeting treatments with risk models, especially when benefit is probably going to be dependent on the absolute risk of adverse outcomes with or without treatment. The ability to systematically take into account the characteristics of an individual patient and their interactions, to consider the risks and benefits of interventions separately if needed, and to provide patients with personalised estimates of their likelihood of benefit is shown using the example of endarterectomy for symptomatic carotid stenosis.