Paul J. Nederkoorn

Post-stroke infection: A systematic review and meta-analysis

Backgroundstroke is the main cause of disability in high-income countries, and ranks second as a cause of death worldwide. Patients with acute stroke are at risk for infections, but reported post-stroke infection rates vary considerably. We performed a systematic review and meta-analysis to estimate the pooled post-stroke infection rate and its effect on outcome.MethodsMEDLINE and EMBASE were searched for studies on post-stroke infection. Cohort studies and randomized clinical trials were included when post-stroke infection rate was reported. Rates of infection were pooled after assessment of heterogeneity. Associations between population- and study characteristics and infection rates were quantified. Finally, we reviewed the association between infection and outcome.Results87 studies were included involving 137817 patients. 8 studies were restricted to patients admitted on the intensive care unit (ICU). There was significant heterogeneity between studies (P < 0.001, I2 = 97%). The overall pooled infection rate was 30% (24-36%); rates of pneumonia and urinary tract infection were 10% (95% confidence interval [CI] 9-10%) and 10% (95%CI 9-12%). For ICU studies, these rates were substantially higher with 45% (95% CI 38-52%), 28% (95%CI 18-38%) and 20% (95%CI 0-40%). Rates of pneumonia were higher in studies that specifically evaluated infections and in consecutive studies. Studies including older patients or more females reported higher rates of urinary tract infection. Pneumonia was significantly associated with death (odds ratio 3.62 (95%CI 2.80-4.68).ConclusionsInfection complicated acute stroke in 30% of patients. Rates of pneumonia and urinary tract infection after stroke were 10%. Pneumonia was associated with death. Our study stresses the need to prevent infections in patients with stroke.

Systematic Review of Computed Tomographic Angiography for Assessment of Carotid Artery Disease

Background and Purpose— To review the literature on the diagnostic accuracy of computed tomographic angiography (CTA) compared with arteriography/intra-arterial digital subtraction angiography as reference standard for assessment of symptomatic carotid artery disease. Methods— The PubMed, MEDLINE, PREMEDLINE, EMBASE, and CINAHL databases were searched to retrieve studies published between 1990 and July 2003, comparing CTA and intra-arterial digital subtraction angiography in patients with symptomatic carotid artery disease that presented raw data for detection of a <70% or 70% to 99% stenosis or an occlusion. Two observers independently assessed methodological quality and constructed 2×2 tables for sensitivity and specificity of CTA for detection of a 70% to 99% stenosis versus <70% stenosis or an occlusion, and for <99% stenosis versus occlusion. A bivariate random effects model was used to calculate the pooled sensitivity and specificity of CTA for detection of these lesions. Results— Some 864 patients (66% male) with a mean age of 66 years were studied in the 28 studies included in the meta-analysis. In all studies, a single-slice CT-scan was used. Only 8 studies satisfied all methodological quality criteria. The pooled sensitivity and specificity for detection of a 70% to 99% stenosis were 85% (95% CI, 79% to 89%) and 93% (95% CI, 89% to 96%), respectively. For detection of an occlusion, the sensitivity and specificity were 97% (95% CI, 93% to 99%) and 99% (95% CI, 98% to 100%), respectively. Incomplete reporting of demographic characteristics and technical differences in the individual studies obstructed a meaningful subgroup analysis. Conclusions— CTA is an accurate modality for detection of severe carotid artery disease, especially for detection of occlusions. The fair methodological quality of the included studies must be taken into account when interpreting these results.

Preoperative Diagnosis of Carotid Artery Stenosis Accuracy of Noninvasive Testing

Background and Purpose— Carotid endarterectomy has been shown to be beneficial in symptomatic patients with a severe stenosis (70% to 99%) of the internal carotid artery (ICA). Digital subtraction angiography (DSA) is the standard of reference in the diagnosis of carotid artery stenosis but has a relatively high complication rate. In a diagnostic study we investigated the accuracy of noninvasive testing compared with DSA. Methods— In a prospective diagnostic study we performed duplex ultrasound (DUS), magnetic resonance angiography (MRA), and DSA on 350 consecutive symptomatic patients. Stenoses were measured with the observers blinded for clinical information and other test results. Separate and combined test results of DUS and MRA were compared with the reference standard DSA. Only the stenosis measurements of the arteries on the symptomatic side were included in the analyses. Results— DUS analyzed with previously defined criteria resulted in a sensitivity of 87.5% (95% CI, 82.1% to 92.9%) and a specificity of 75.7% (95% CI, 69.3% to 82.2%) in identifying severe ICA stenosis (70% to 99%). Stenosis measurements on MRA yielded a sensitivity of 92.2% (95% CI, 86.2% to 96.2%) and a specificity of 75.7% (95% CI, 68.6% to 82.5%). When we combined MRA and DUS results, agreement between these 2 modalities (84% of patients) gave a sensitivity of 96.3% (95% CI, 90.8% to 99.0%) and a specificity of 80.2% (95% CI, 73.1% to 87.3%) for identifying severe stenosis. Conclusions— MRA showed a slightly better accuracy than DUS in the diagnosis of carotid artery stenosis. To achieve the best accuracy, however, both tests should be performed subsequently.

Platelet transfusion versus standard care after acute stroke due to spontaneous cerebral haemorrhage associated with antiplatelet therapy (PATCH): a randomised, open-label, phase 3 trial

BACKGROUND Platelet transfusion after acute spontaneous primary intracerebral haemorrhage in people taking antiplatelet therapy might reduce death or dependence by reducing the extent of the haemorrhage. We aimed to investigate whether platelet transfusion with standard care, compared with standard care alone, reduced death or dependence after intracerebral haemorrhage associated with antiplatelet therapy use. METHODS We did this multicentre, open-label, masked-endpoint, randomised trial at 60 hospitals in the Netherlands, UK, and France. We enrolled adults within 6 h of supratentorial intracerebral haemorrhage symptom onset if they had used antiplatelet therapy for at least 7 days beforehand and had a Glasgow Coma Scale score of at least 8. With use of a secure web-based system that concealed allocation and used biased coin randomisation, study collaborators randomly assigned participants (1:1; stratified by hospital and type of antiplatelet therapy) to receive either standard care or standard care with platelet transfusion within 90 min of diagnostic brain imaging. Participants and local investigators giving interventions were not masked to treatment allocation, but allocation was concealed from outcome assessors and investigators analysing data. The primary outcome was shift towards death or dependence rated on the modified Rankin Scale (mRS) at 3 months, and analysed by ordinal logistic regression, adjusted for stratification variables and the Intracerebral Haemorrhage Score. The primary analysis was done in the intention-to-treat population and safety analyses were done in the intention-to-treat and as-treated populations. This trial is registered with the Netherlands Trial Register, number NTR1303, and is now closed. FINDINGS Between Feb 4, 2009, and Oct 8, 2015, 41 sites enrolled 190 participants. 97 participants were randomly assigned to platelet transfusion and 93 to standard care. The odds of death or dependence at 3 months were higher in the platelet transfusion group than in the standard care group (adjusted common odds ratio 2·05, 95% CI 1·18-3·56; p=0·0114). 40 (42%) participants who received platelet transfusion had a serious adverse event during their hospital stay, as did 28 (29%) who received standard care. 23 (24%) participants assigned to platelet transfusion and 16 (17%) assigned to standard care died during hospital stay. INTERPRETATION Platelet transfusion seems inferior to standard care for people taking antiplatelet therapy before intracerebral haemorrhage. Platelet transfusion cannot be recommended for this indication in clinical practice. FUNDING The Netherlands Organisation for Health Research and Development, Sanquin Blood Supply, Chest Heart and Stroke Scotland, French Ministry of Health.

Safety of Thrombolysis in Stroke Mimics Results From a Multicenter Cohort Study

Background and Purpose— Intravenous thrombolysis for acute ischemic stroke is beneficial within 4.5 hours of symptom onset, but the effect rapidly decreases over time, necessitating quick diagnostic in-hospital work-up. Initial time strain occasionally results in treatment of patients with an alternate diagnosis (stroke mimics). We investigated whether intravenous thrombolysis is safe in these patients. Methods— In this multicenter observational cohort study containing 5581 consecutive patients treated with intravenous thrombolysis, we determined the frequency and the clinical characteristics of stroke mimics. For safety, we compared the symptomatic intracranial hemorrhage (European Cooperative Acute Stroke Study II [ECASS-II] definition) rate of stroke mimics with ischemic strokes. Results— One hundred stroke mimics were identified, resulting in a frequency of 1.8% (95% confidence interval, 1.5–2.2). Patients with a stroke mimic were younger, more often female, and had fewer risk factors except smoking and previous stroke or transient ischemic attack. The symptomatic intracranial hemorrhage rate in stroke mimics was 1.0% (95% confidence interval, 0.0–5.0) compared with 7.9% (95% confidence interval, 7.2–8.7) in ischemic strokes. Conclusions— In experienced stroke centers, among patients treated with intravenous thrombolysis, only a few had a final diagnosis other than stroke. The complication rate in these stroke mimics was low.

Safety and Functional Outcome of Thrombolysis in Dissection-Related Ischemic Stroke A Meta-Analysis of Individual Patient Data

Background and Purpose— The safety and efficacy of thrombolysis in cervical artery dissection (CAD) are controversial. The aim of this meta-analysis was to pool all individual patient data and provide a valid estimate of safety and outcome of thrombolysis in CAD. Methods— We performed a systematic literature search on intravenous and intra-arterial thrombolysis in CAD. We calculated the rates of pooled symptomatic intracranial hemorrhage and mortality and indirectly compared them with matched controls from the Safe Implementation of Thrombolysis in Stroke–International Stroke Thrombolysis Register. We applied multivariate regression models to identify predictors of excellent (modified Rankin Scale=0 to 1) and favorable (modified Rankin Scale=0 to 2) outcome. Results— We obtained individual patient data of 180 patients from 14 retrospective series and 22 case reports. Patients were predominantly female (68%), with a mean±SD age of 46±11 years. Most patients presented with severe stroke (median National Institutes of Health Stroke Scale score=16). Treatment was intravenous thrombolysis in 67% and intra-arterial thrombolysis in 33%. Median follow-up was 3 months. The pooled symptomatic intracranial hemorrhage rate was 3.1% (95% CI, 1.3 to 7.2). Overall mortality was 8.1% (95% CI, 4.9 to 13.2), and 41.0% (95% CI, 31.4 to 51.4) had an excellent outcome. Stroke severity was a strong predictor of outcome. Overlapping confidence intervals of end points indicated no relevant differences with matched controls from the Safe Implementation of Thrombolysis in Stroke–International Stroke Thrombolysis Register. Conclusions— Safety and outcome of thrombolysis in patients with CAD-related stroke appear similar to those for stroke from all causes. Based on our findings, thrombolysis should not be withheld in patients with CAD.

Time to Reperfusion and Treatment Effect for Acute Ischemic Stroke: A Randomized Clinical Trial

IMPORTANCE Intra-arterial treatment (IAT) for acute ischemic stroke caused by intracranial arterial occlusion leads to improved functional outcome in patients treated within 6 hours after onset. The influence of treatment delay on treatment effect is not yet known. OBJECTIVE To evaluate the influence of time from stroke onset to the start of treatment and from stroke onset to reperfusion on the effect of IAT. DESIGN, SETTING, AND PARTICIPANTS The Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands (MR CLEAN) was a multicenter, randomized clinical open-label trial of IAT vs no IAT in 500 patients. The time to the start of treatment was defined as the time from onset of symptoms to groin puncture (TOG). The time from onset of treatment to reperfusion (TOR) was defined as the time to reopening the vessel occlusion or the end of the procedure in cases for which reperfusion was not achieved. Data were collected from December 3, 2010, to June 3, 2014, and analyzed (intention to treat) from July 1, 2014, to September 19, 2015. MAIN OUTCOMES AND MEASURES Main outcome was the modified Rankin Scale (mRS) score for functional outcome (range, 0 [no symptoms] to 6 [death]). Multiple ordinal logistic regression analysis estimated the effect of treatment and tested for the interaction of time to randomization, TOG, and TOR with treatment. The effect of treatment as a risk difference on reaching independence (mRS score, 0-2) was computed as a function of TOG and TOR. Calculations were adjusted for age, National Institutes of Health Stroke Scale score, previous stroke, atrial fibrillation, diabetes mellitus, and intracranial arterial terminus occlusion. RESULTS Among 500 patients (58% male; median age, 67 years), the median TOG was 260 (interquartile range [IQR], 210-311) minutes; median TOR, 340 (IQR, 274-395) minutes. An interaction between TOR and treatment (P = .04) existed, but not between TOG and treatment (P = .26). The adjusted risk difference (95% CI) was 25.9% (8.3%-44.4%) when reperfusion was reached at 3 hours, 18.8% (6.6%-32.6%) at 4 hours, and 6.7% (0.4%-14.5%) at 6 hours. CONCLUSION AND RELEVANCE For every hour of reperfusion delay, the initially large benefit of IAT decreases; the absolute risk difference for a good outcome is reduced by 6% per hour of delay. Patients with acute ischemic stroke require immediate diagnostic workup and IAT in case of intracranial arterial vessel occlusion. TRIAL REGISTRATION trialregister.nl Identifier: NTR1804.

Preventive Antibiotics for Infections in Acute Stroke: A Systematic Review and Meta-analysis

OBJECTIVE To provide a systematic overview and meta-analysis of randomized clinical trials evaluating preventive antibiotics in patients with acute stroke. DATA SOURCES The MEDLINE (1966-February 2009) and Cochrane databases and reference lists of retrieved articles. STUDY SELECTION Randomized controlled trials on preventive antibiotic treatment in stroke. For inclusion, at least case fatality or infection rate had to be recorded. DATA EXTRACTION Each study was scored for methodological key issues and appraised by the Jadad scale. We extracted the data using a predetermined protocol and included all patients who were randomized or who started therapy in an intent-to-treat analysis. DATA SYNTHESIS We identified 4 randomized clinical trials including 426 patients; 94% had ischemic stroke. Study interventions were fluoroquinolones in 2 and tetracycline or a combination of beta-lactam antibiotic with beta-lactamase inhibitor in 1. Therapy was started within 24 hours of stroke onset. Duration of therapy varied between 3 and 5 days. The methodological quality ranged from 2 to 5 on the Jadad scale, and studies were subject to potential bias. The proportion of patients with infection was significantly smaller in the antibiotic group than in the placebo/control group (32 of 136 [23.5%] vs 53 of 139 [38.1%] patients). The pooled odds ratio for infection was 0.44 (95% confidence interval, 0.23-0.86). Ten of 210 patients (4.8%) in the antibiotic group died, compared with 13 of 216 (6.0%) in the placebo/control group. The pooled odds ratio for mortality was 0.63 (95% confidence interval, 0.22-1.78). No major harm or toxicity was reported. CONCLUSIONS In adults with acute stroke, preventive antibiotics reduced the risk of infection, but did not reduce mortality. The observed effect warrants evaluation of preventive antibiotics in large stroke trials.

Minor Head Injury: CT-based Strategies for Management—A Cost-effectiveness Analysis

PURPOSE To compare the cost-effectiveness of using selective computed tomographic (CT) strategies with that of performing CT in all patients with minor head injury (MHI). MATERIALS AND METHODS The internal review board approved the study; written informed consent was obtained from all interviewed patients. Five strategies were evaluated, with CT performed in all patients with MHI; selectively according to the New Orleans criteria (NOC), Canadian CT head rule (CCHR), or CT in head injury patients (CHIP) rule; or in no patients. A decision tree was used to analyze short-term costs and effectiveness, and a Markov model was used to analyze long-term costs and effectiveness. n-Way and probabilistic sensitivity analyses and value-of-information (VOI) analysis were performed. Data from the multicenter CHIP Study involving 3181 patients with MHI were used. Outcome measures were first-year and lifetime costs, quality-adjusted life-years, and incremental cost-effectiveness ratios. RESULTS Study results showed that performing CT selectively according to the CCHR or the CHIP rule could lead to substantial U.S. cost savings (

Cognition after carotid endarterectomy or stenting A randomized comparison

120 million and