Development and internal validation of a prediction rule for post-stroke infection and post-stroke pneumonia in acute stroke patients

Introduction Patients with acute stroke are at high risk for infection. These infections are associated with unfavourable outcome after stroke. A prediction rule can identify the patients at the highest risk for strategies to prevent infection. We aim to develop a prediction rule for post-stroke pneumonia and other infections in patients with acute stroke. Patients and methods We used data from the Preventive Antibiotics in Stroke Study, a multicentre randomised trial comparing preventive ceftriaxone vs. standard stroke care in patients with acute stroke. Possible predictors for post-stroke pneumonia or infection were selected from the literature. Backward elimination logistic regression analysis was used to construct prediction rules for pneumonia or infection. Internal validation was performed and a risk chart was constructed. We adjusted for preventive antibiotic use. Results Pneumonia was diagnosed in 159 of the 2538 included patients, and infection in 348. Pneumonia was predicted by higher age, male sex, pre-stroke disability, medical history of chronic obstructive pulmonary disease, more severe stroke, dysphagia and intracerebral haemorrhage (rather than ischaemic stroke). Infections were predicted by higher age, male sex, history of diabetes, chronic obstructive pulmonary disease, more severe stroke, dysphagia, use of bladder catheter, preventive antibiotic use and intracerebral

Predicting the presence of macrovascular causes in non-traumatic intracerebral haemorrhage: the DIAGRAM prediction score

Paroxysmal Cerebral Disorder

Bleeding on antithrombotic treatment in secondary stroke prevention

Stroke is a major cause of death and adult disability world wide. Approximately 20-30% of all strokes occur in patients with a previous stroke. Secondary prevention is essential to reduce risk of recurrence after a first stroke, and antithrombotic treatment is one of the key interventions in secondary prevention. However, bleeding is an important and potentially life-threatening side effect of antithrombotic drugs. The main aim of this thesis is to identify which patients are at high risk of bleeding on antithrombotic treatment and to investigate whether antithrombotic treatment can be optimised based on bleeding risk assessment. We developed the S2TOP-BLEED score to predict an individuals’ risk of major bleeding on antiplatelet treatment. The score is based on ten readily available characteristics: age, sex, Asian ethnicity, smoking, hypertension, diabetes, prior stroke, BMI, outcome on the modified Rankin scale and type of antiplatelet treatment. The score showed modest discriminatory performance in the development cohort and two subsequent external validation cohorts, but accurate calibration. In order to inform treatment decisions, the harms of antithrombotic treatment should be weighed against the benefits. We observed that those patients at highest risk of a major bleeding event were also at highest risk for recurrent ischaemic events. The risk reduction in ischaemic events was larger than the increase in major bleeds, irrespective of bleeding risk category. This was true both for patients on antiplatelet treatment and on oral anticoagulants after a TIA or stroke. We conclude that bleeding risk stratification should not guide decisions on antithrombotic treatment following a TIA or ischaemic stroke. However, bleeding risk assessment might still be useful to identify patients in whom preventive treatment should be considered. We subsequently investigated timing of bleeding on antiplatelet treatment and observed that risk of major and gastro-intestinal bleeding is highest early after start of dual antiplatelet therapy, and declines after the first 30 days. The risk of intracranial haemorrhage was stable over time. Blood pressure control is another important aspect of secondary stroke prevention, but uncertainty exists regarding the optimal target blood pressure. We studied the association between blood pressure and the risk of intracerebral haemorrhage after stroke and observed that risk of intracerebral haemorrhage increased with increasing blood pressure levels. Further studies are needed to establish whether blood pressure targets below 140 mmHg systolic confer additional benefit in terms of prevention of intracerebral haemorrhage. Last, we developed the DIAGRAM risk score to predict which patients have a high likelihood of an underlying macrovascular abnormality as cause for an intracerebral haemorrhage. This score may facilitate selection of patients for additional imaging following intracerebral haemorrhage, but requires further validation to confirm its robustness