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Introduction Unruptured intracranial aneurysms (UIA) are common in the adult population, but only a relatively small proportion will rupture. It is therefore essential to have accurate estimates of rupture risk to target treatment towards those who stand to benefit and avoid exposing patients to the risks of unnecessary treatment. The best available UIA natural history data are the PHASES study. However, this has never been validated and given the known heterogeneity in the populations, methods and biases of the constituent studies, there is a need to do so. There are also many potential predictors not considered in PHASES that require evaluation, and the estimated rupture risk is largely based on short-term follow-up (mostly 1 year). The aims of this study are to: (1) test the accuracy of PHASES in a UK population, (2) evaluate additional predictors of rupture and (3) assess long-term UIA rupture rates.Methods and analysis The Risk of Aneurysm Rupture study is a longitudinal multicentre study that will identify patients with known UIA seen in neurosurgery units. Patients will have baseline demographics and aneurysm characteristics collected by their neurosurgery unit and then a single aggregated national cohort will be linked to databases of hospital admissions and deaths to identify all patients who may have subsequently suffered a subarachnoid haemorrhage. All matched admissions and deaths will be checked against medical records to confirm the diagnosis of aneurysmal subarachnoid haemorrhage. The target sample size is 20 000 patients. The primary outcome will be aneurysm rupture resulting in hospital admission or death. Cox regression models will be built to test each of the study’s aims.Ethics and dissemination Ethical approval has been given by South Central Hampshire A Research Ethics Committee (21SC0064) and Confidentiality Advisory Group support (21CAG0033) provided under Section 251 of the NHS Act 2006. The results will be disseminated in peer-reviewed journals.Trial registration number ISRCTN17658526.

Abstract Background Heart failure (HF) is a major global challenge, emphasised by its designation as the leading cause of hospitalisation in those aged 65 and above. Approximately half of all patients with HF have concurrent iron deficiency (ID) regardless of anaemia status. In HF, iron deficiency is independently associated with higher rates of hospitalisation and death, lower exercise capacity, and poorer quality-of-life than in patients without iron deficiency. With such consequences, several studies have investigated whether correcting ID can improve HF outcomes. Main body. As of 1st June 2021, seven randomised controlled trials have explored the use of intravenous (IV) iron in patients with HF and ID, along with various meta-analyses including an individual patient data meta-analysis, all of which are discussed in this review. IV iron was well tolerated, with a comparable frequency of adverse events to placebo. In the context of heart failure with reduced ejection fraction (HFrEF), IV iron reduces the risk of hospitalisation for HF, and improves New York Heart Association (NYHA) functional class, quality-of-life, and exercise capacity (as measured by 6-min walk test (6MWT)) distance and peak oxygen consumption. However, the effect of IV iron on mortality is uncertain. Finally, the evidence for IV iron in patients with acute decompensated heart failure, or heart failure with preserved ejection fraction (HFpEF) is limited. Conclusions IV iron improves some outcomes in patients with HFrEF and ID. Patients with HFrEF should be screened for ID, defined as ferritin