Update of the Preventive Antibiotics in Stroke Study (PASS): Statistical analysis plan

Background: Infections occur in 30% of stroke patients and are associated with unfavorable outcomes. Preventive antibiotic therapy lowers the infection rate after stroke, but the effect of preventive antibiotic treatment on functional outcome in patients with stroke is unknown. The PASS is a multicenter, prospective, phase three, randomized, open-label, blinded end-point (PROBE) trial of preventive antibiotic therapy in acute stroke. Patients are randomly assigned to either ceftriaxone at a dose of 2 g, given every 24 h intravenously for 4 days, in addition to standard stroke-unit care, or standard stroke-unit care without preventive antibiotic therapy. The aim of this study is to assess whether preventive antibiotic treatment improves functional outcome at 3 months by preventing infections. This paper presents in detail the statistical analysis plan (SAP) of the Preventive Antibiotics in Stroke Study (PASS) and was submitted while the investigators were st

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

Infliximab treatment in pathology-confirmed neurosarcoidosis

OBJECTIVE: To assess the efficacy and risks of treatment with infliximab (anti-tumor necrosis factor alpha) in pathology-confirmed neurosarcoidosis. METHODS: In a retrospective study in 2 tertiary referral centers in the Netherlands, we analyzed clinical characteristics, complications, and outcome of patients with neurosarcoidosis treated with infliximab. RESULTS: Twenty-eight patients were identified with a mean age of 42 years. Neurosarcoidosis presented with a cerebral parenchymal localization in 16 (59%), pituitary gland/hypothalamic sarcoidosis in 15 (54%), peripheral nerve involvement in 12 (43%), and chronic meningitis in 11 patients (41%). Initial treatment response after the start of infliximab was complete remission in 6 (21%) and improvement in 14 (50%), whereas 7 patients had stable disease (25%), and 1 (4%) deteriorated and died. At the end of follow-up, with a median of 32 months, 5 patients (18%) had died, and 2 (40%) were using infliximab at the time of death. Tapering or discontinuation of corticosteroids without a relapse was achieved in 19 of 28 patients (68%). In patients with decreasing dosing or discontinuation of infliximab, a relapse occurred in 5 of 19 patients (26%). Complications of infliximab were reported in 10 of 28 patients (36%) and mainly consisted of infections in 8 (29%). CONCLUSION: Infliximab is an effective treatment in neurosarcoidosis leading to remission or improvement in 70%. The mortality rate in infliximab-treated patients was substantial, indicating the severity of disease and treatment-associated complications. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that in people with pathology-confirmed neurosarcoidosis, infliximab is beneficial