C-Reactive Protein, Interleukin-6, and Vascular Recurrence After Stroke: An Individual Participant Data Meta-Analysis.

BACKGROUND: Anti-inflammatory therapies reduce recurrent vascular events in coronary disease. Existing studies have reported highly conflicting findings for the association of blood inflammatory markers with vascular recurrence after stroke leading to uncertainty about the potential of anti-inflammatory therapies after stroke and no consensus about the utility of measurement of inflammatory markers in current guidelines. METHODS: We investigated the association between hsCRP (high-sensitivity C-reactive protein), IL-6 (interluekin-6), and recurrent major adverse cardiovascular events (MACE), and stroke from individual participant data from 8420 patients with ischemic stroke/transient ischemic attack from 10 prospective studies. We did within-study multivariable regression analyses and then combined adjusted risk ratio (RR) by random-effects meta-analysis. RESULTS: During 18 920 person-years of follow-up, 1407 (16.7% [95% CI, 15.9-17.5]) patients had MACE and 1191 (14.1% [95% CI, 13.4-14.9]) patients had recurrent stroke. On bivariate analysis, baseline IL-6 was associated with MACE (RR, 1.26 [95% CI, 1.10-1.43]) and recurrent stroke (RR, 1.18 [95% CI, 1.05-1.32]), per unit increase logeIL-6. Similar associations were observed for hsCRP (MACE RR, 1.19 [95% CI, 1.09-1.29]; recurrent stroke RR, 1.12 [95% CI, 1.04-1.21], per unit increase logehsCRP). After adjustment for vascular risk factors and treatment, independent associations remained with MACE (IL-6, RR, 1.12 [95% CI, 1.04-1.21]; hsCRP, RR, 1.09 [95% CI, 1.04-1.15]) and recurrent stroke (IL-6, RR, 1.09 [95% CI, 1.00-1.19]; hsCRP, RR, 1.05 [95% CI, 1.00-1.11]). Comparing the top with the bottom quarters (Q4 versus Q1), IL-6 (RR, 1.35 [95% CI, 1.09-1.67]) and hsCRP (RR, 1.31 [95% CI, 1.07-1.61]) were associated with MACE after adjustment. Similar results were observed for recurrent stroke for IL-6 (RR, 1.33 [95% CI, 1.08-1.65]) but not hsCRP (RR, 1.16 [95% CI, 0.93-1.43]). CONCLUSIONS: Blood markers of inflammation were independently associated with vascular recurrence after stroke, strengthening the rationale for randomized trials of anti-inflammatory therapies for secondary prevention after ischemic stroke/TIA.

Editor's Choice - Effect of Carotid Endarterectomy on 20 Year Incidence of Recorded Dementia: A Randomised Trial.

OBJECTIVE: Stroke and carotid atherosclerosis are associated with dementia. Carotid endarterectomy (CEA) reduces stroke risk, although its effect on later dementia is uncertain. Participants in the Asymptomatic Carotid Surgery Trial (ACST-1), randomly allocated to immediate vs. deferral of CEA (i.e., no intervention unless or until triggered by ipsilateral transient ischaemic attack or stroke), were followed, to study effects on dementia. METHODS: From 1993 to 2003, ACST-1 included 3 120 participants with asymptomatic tight carotid stenosis. All UK and Swedish patients (n = 1 601; 796 immediate vs. 805 deferral) were followed with trial records, national electronic health record linkage, and (UK only) by post and telephone. Cumulative incidence and competing risk analyses were used to measure the effects of risk factors and CEA on dementia risk. Intention to treat analyses yielded hazard ratios (HRs; immediate vs. deferral) of dementia. RESULTS: The median follow up was 19.4 years (interquartile range 16.9 - 21.7). Dementia was recorded in 107 immediate CEA patients and 115 allocated delayed surgery; 1 290 patients died (1 091 [538 vs. 536] before any dementia diagnosis). Dementia incidence rose with age and with female sex (men: 8.3% aged < 70 years at trial entry vs. 15.1% aged ≥ 70; women: 15.1% aged < 70 years at trial entry vs. 22.4% aged ≥ 70 years) and was higher in those with pre-existing cerebral infarction (silent or with prior symptoms; 20.2% vs. 13.6%). Dementia risk was similar in both randomised groups: 6.7% vs. 6.6% at 10 years and 14.3% vs. 15.5% at 20 years, respectively. The dementia HR was 0.98 (95% confidence interval [CI] 0.75 - 1.28; p = .89), with no heterogeneity in the neutral effect of immediate CEA on dementia related to age, carotid stenosis, blood pressure, diabetes, country of residence, or medical treatments at trial entry (heterogeneity values p > .05). CONCLUSION: CEA was not associated with significant reductions in the long term hazards of dementia, but the CI did not exclude a proportional benefit or hazard of about 25%.

Association of COVID-19 vaccines ChAdOx1 and BNT162b2 with major venous, arterial, or thrombocytopenic events: A population-based cohort study of 46 million adults in England.

BACKGROUND: Thromboses in unusual locations after the Coronavirus Disease 2019 (COVID-19) vaccine ChAdOx1-S have been reported, although their frequency with vaccines of different types is uncertain at a population level. The aim of this study was to estimate the population-level risks of hospitalised thrombocytopenia and major arterial and venous thromboses after COVID-19 vaccination. METHODS AND FINDINGS: In this whole-population cohort study, we analysed linked electronic health records from adults living in England, from 8 December 2020 to 18 March 2021. We estimated incidence rates and hazard ratios (HRs) for major arterial, venous, and thrombocytopenic outcomes 1 to 28 and >28 days after first vaccination dose for ChAdOx1-S and BNT162b2 vaccines. Analyses were performed separately for ages <70 and ≥70 years and adjusted for age, age2, sex, ethnicity, and deprivation. We also prespecified adjustment for anticoagulant medication, combined oral contraceptive medication, hormone replacement therapy medication, history of pulmonary embolism or deep vein thrombosis, and history of coronavirus infection in analyses of venous thrombosis; and diabetes, hypertension, smoking, antiplatelet medication, blood pressure lowering medication, lipid lowering medication, anticoagulant medication, history of stroke, and history of myocardial infarction in analyses of arterial thromboses. We selected further covariates with backward selection. Of 46 million adults, 23 million (51%) were women; 39 million (84%) were <70; and 3.7 million (8.1%) Asian or Asian British, 1.6 million (3.5%) Black or Black British, 36 million (79%) White, 0.7 million (1.5%) mixed ethnicity, and 1.5 million (3.2%) were of another ethnicity. Approximately 21 million (46%) adults had their first vaccination between 8 December 2020 and 18 March 2021. The crude incidence rates (per 100,000 person-years) of all venous events were as follows: prevaccination, 140 [95% confidence interval (CI): 138 to 142]; ≤28 days post-ChAdOx1-S, 294 (281 to 307); >28 days post-ChAdOx1-S, 359 (338 to 382), ≤28 days post-BNT162b2-S, 241 (229 to 253); >28 days post-BNT162b2-S 277 (263 to 291). The crude incidence rates (per 100,000 person-years) of all arterial events were as follows: prevaccination, 546 (95% CI: 541 to 555); ≤28 days post-ChAdOx1-S, 1,211 (1,185 to 1,237); >28 days post-ChAdOx1-S, 1678 (1,630 to 1,726), ≤28 days post-BNT162b2-S, 1,242 (1,214 to 1,269); >28 days post-BNT162b2-S, 1,539 (1,507 to 1,572). Adjusted HRs (aHRs) 1 to 28 days after ChAdOx1-S, compared with unvaccinated rates, at ages <70 and ≥70 years, respectively, were 0.97 (95% CI: 0.90 to 1.05) and 0.58 (0.53 to 0.63) for venous thromboses, and 0.90 (0.86 to 0.95) and 0.76 (0.73 to 0.79) for arterial thromboses. Corresponding aHRs for BNT162b2 were 0.81 (0.74 to 0.88) and 0.57 (0.53 to 0.62) for venous thromboses, and 0.94 (0.90 to 0.99) and 0.72 (0.70 to 0.75) for arterial thromboses. aHRs for thrombotic events were higher at younger ages for venous thromboses after ChAdOx1-S, and for arterial thromboses after both vaccines. Rates of intracranial venous thrombosis (ICVT) and of thrombocytopenia in adults aged <70 years were higher 1 to 28 days after ChAdOx1-S (aHRs 2.27, 95% CI: 1.33 to 3.88 and 1.71, 1.35 to 2.16, respectively), but not after BNT162b2 (0.59, 0.24 to 1.45 and 1.00, 0.75 to 1.34) compared with unvaccinated. The corresponding absolute excess risks of ICVT 1 to 28 days after ChAdOx1-S were 0.9 to 3 per million, varying by age and sex. The main limitations of the study are as follows: (i) it relies on the accuracy of coded healthcare data to identify exposures, covariates, and outcomes; (ii) the use of primary reason for hospital admission to measure outcome, which improves the positive predictive value but may lead to an underestimation of incidence; and (iii) potential unmeasured confounding. CONCLUSIONS: In this study, we observed increases in rates of ICVT and thrombocytopenia after ChAdOx1-S vaccination in adults aged <70 years that were small compared with its effect in reducing COVID-19 morbidity and mortality, although more precise estimates for adults aged <40 years are needed. For people aged ≥70 years, rates of arterial or venous thrombotic events were generally lower after either vaccine compared with unvaccinated, suggesting that either vaccine is suitable in this age group.

European Stroke Organisation (ESO)-European Society for Minimally Invasive Neurological Therapy (ESMINT) expedited recommendation on indication for intravenous thrombolysis before mechanical thrombectomy in patients with acute ischemic stroke and anterior circulation large vessel occlusion.

Six randomized controlled clinical trials have assessed whether mechanical thrombectomy (MT) alone is non-inferior to intravenous thrombolysis (IVT) plus MT within 4.5 hours of symptom onset in patients with anterior circulation large vessel occlusion (LVO) ischemic stroke and no contraindication to IVT. An expedited recommendation process was initiated by the European Stroke Organisation (ESO) and conducted with the European Society of Minimally Invasive Neurological Therapy (ESMINT) according to ESO standard operating procedure based on the GRADE system. We identified two relevant Population, Intervention, Comparator, Outcome (PICO) questions, performed systematic reviews and meta-analyses of the literature, assessed the quality of the available evidence, and wrote evidence-based recommendations. Expert opinion was provided if insufficient evidence was available to provide recommendations based on the GRADE approach.For stroke patients with anterior circulation LVO directly admitted to a MT-capable center ('mothership') within 4.5 hours of symptom onset and eligible for both treatments, we recommend IVT plus MT over MT alone (moderate evidence, strong recommendation). MT should not prevent the initiation of IVT, nor should IVT delay MT. In stroke patients with anterior circulation LVO admitted to a center without MT facilities and eligible for IVT ≤4.5 hours and MT, we recommend IVT followed by rapid transfer to a MT capable-center ('drip-and-ship') in preference to omitting IVT (low evidence, strong recommendation). Expert consensus statements on ischemic stroke on awakening from sleep are also provided. Patients with anterior circulation LVO stroke should receive IVT in addition to MT if they have no contraindications to either treatment.

The reporting quality of natural language processing studies: systematic review of studies of radiology reports.

BACKGROUND: Automated language analysis of radiology reports using natural language processing (NLP) can provide valuable information on patients' health and disease. With its rapid development, NLP studies should have transparent methodology to allow comparison of approaches and reproducibility. This systematic review aims to summarise the characteristics and reporting quality of studies applying NLP to radiology reports. METHODS: We searched Google Scholar for studies published in English that applied NLP to radiology reports of any imaging modality between January 2015 and October 2019. At least two reviewers independently performed screening and completed data extraction. We specified 15 criteria relating to data source, datasets, ground truth, outcomes, and reproducibility for quality assessment. The primary NLP performance measures were precision, recall and F1 score. RESULTS: Of the 4,836 records retrieved, we included 164 studies that used NLP on radiology reports. The commonest clinical applications of NLP were disease information or classification (28%) and diagnostic surveillance (27.4%). Most studies used English radiology reports (86%). Reports from mixed imaging modalities were used in 28% of the studies. Oncology (24%) was the most frequent disease area. Most studies had dataset size > 200 (85.4%) but the proportion of studies that described their annotated, training, validation, and test set were 67.1%, 63.4%, 45.7%, and 67.7% respectively. About half of the studies reported precision (48.8%) and recall (53.7%). Few studies reported external validation performed (10.8%), data availability (8.5%) and code availability (9.1%). There was no pattern of performance associated with the overall reporting quality. CONCLUSIONS: There is a range of potential clinical applications for NLP of radiology reports in health services and research. However, we found suboptimal reporting quality that precludes comparison, reproducibility, and replication. Our results support the need for development of reporting standards specific to clinical NLP studies.

A validated natural language processing algorithm for brain imaging phenotypes from radiology reports in UK electronic health records.

BACKGROUND: Manual coding of phenotypes in brain radiology reports is time consuming. We developed a natural language processing (NLP) algorithm to enable automatic identification of brain imaging in radiology reports performed in routine clinical practice in the UK National Health Service (NHS). METHODS: We used anonymized text brain imaging reports from a cohort study of stroke/TIA patients and from a regional hospital to develop and test an NLP algorithm. Two experts marked up text in 1692 reports for 24 cerebrovascular and other neurological phenotypes. We developed and tested a rule-based NLP algorithm first within the cohort study, and further evaluated it in the reports from the regional hospital. RESULTS: The agreement between expert readers was excellent (Cohen's κ =0.93) in both datasets. In the final test dataset (n = 700) in unseen regional hospital reports, the algorithm had very good performance for a report of any ischaemic stroke [sensitivity 89% (95% CI:81-94); positive predictive value (PPV) 85% (76-90); specificity 100% (95% CI:0.99-1.00)]; any haemorrhagic stroke [sensitivity 96% (95% CI: 80-99), PPV 72% (95% CI:55-84); specificity 100% (95% CI:0.99-1.00)]; brain tumours [sensitivity 96% (CI:87-99); PPV 84% (73-91); specificity: 100% (95% CI:0.99-1.00)] and cerebral small vessel disease and cerebral atrophy (sensitivity, PPV and specificity all > 97%). We obtained few reports of subarachnoid haemorrhage, microbleeds or subdural haematomas. In 110,695 reports from NHS Tayside, atrophy (n = 28,757, 26%), small vessel disease (15,015, 14%) and old, deep ischaemic strokes (10,636, 10%) were the commonest findings. CONCLUSIONS: An NLP algorithm can be developed in UK NHS radiology records to allow identification of cohorts of patients with important brain imaging phenotypes at a scale that would otherwise not be possible.

Potentially serious incidental findings on brain and body magnetic resonance imaging of apparently asymptomatic adults: systematic review and meta-analysis.

OBJECTIVES: To determine prevalence and types of potentially serious incidental findings on magnetic resonance imaging (MRI) in apparently asymptomatic adults, describe factors associated with potentially serious incidental findings, and summarise information on follow-up and final diagnoses. DESIGN: Systematic review and meta-analyses. DATA SOURCES: Citation searches of relevant articles and authors' files in Medline and Embase (from inception to 25 April 2017). REVIEW METHODS: Eligible studies included prevalence and types of incidental findings detected among apparently asymptomatic adults undergoing MRI of the brain, thorax, abdomen, or brain and body. Data on study population and methods, prevalence and types of incidental findings, and final diagnoses were extracted. Pooled prevalence was estimated by random effects meta-analysis, and heterogeneity by τ2 statistics. MAIN OUTCOME MEASURES: Prevalence of potentially serious incidental findings on MRI of the brain, thorax, abdomen, and brain and body. RESULTS: Of 5905 retrieved studies, 32 (0.5%) met the inclusion criteria (n=27 643 participants). Pooled prevalence of potentially serious incidental findings was 3.9% (95% confidence interval 0.4% to 27.1%) on brain and body MRI, 1.4% (1.0% to 2.1%) on brain MRI, 1.3% (0.2% to 8.1%) on thoracic MRI, and 1.9% (0.3% to 12.0%) on abdominal MRI. Pooled prevalence rose after including incidental findings of uncertain potential seriousness (12.8% (3.9% to 34.3%), 1.7% (1.1% to 2.6%), 3.0% (0.8% to 11.3%), and 4.5% (1.5% to 12.9%), respectively). There was generally substantial heterogeneity among included studies. About half the potentially serious incidental findings were suspected malignancies (brain, 0.6% (95% confidence interval 0.4% to 0.9%); thorax, 0.6% (0.1% to 3.1%); abdomen, 1.3% (0.2% to 9.3%); brain and body, 2.3% (0.3% to 15.4%)). There were few informative data on potential sources of between-study variation or factors associated with potentially serious incidental findings. Limited data suggested that relatively few potentially serious incidental findings had serious final diagnoses (48/234, 20.5%). CONCLUSIONS: A substantial proportion of apparently asymptomatic adults will have potentially serious incidental findings on MRI, but little is known of their health consequences. Systematic, long term follow-up studies are needed to better inform on these consequences and the implications for policies on feedback of potentially serious incidental findings. SYSTEMATIC REVIEW REGISTRATION: Prospero CRD42016029472.

Cognition in chronic kidney disease: a systematic review and meta-analysis.

BACKGROUND: Cognitive impairment is common in people with chronic kidney disease (CKD) and associated with increased morbidity and mortality. Subtle changes can impact engagement with healthcare, comprehension, decision-making, and medication adherence. We aimed to systematically summarise evidence of cognitive changes in CKD. METHODS: We searched MEDLINE (March 2016) for cross-sectional, cohort or randomised studies that measured cognitive function in people with CKD (PROSPERO, registration number CRD42014015226). The CKD population included people with eGFR < 60 mL/min/1.73 m2, not receiving renal replacement therapy, in any research setting. We conducted a meta-analysis using random effects, expressed as standardised mean differences (SMD) with 95% confidence intervals (CI). Outcomes were performance in eight cognitive domains. Bias was assessed with the Newcastle-Ottawa Scale (NOS). RESULTS: We identified 44 studies reporting sufficient data for synthesis (51,575 participants). Mean NOS score for cohort studies was 5.8/9 and for cross-sectional 5.4/10. Studies were deficient in NOS outcome and selection due to poor methods reporting and in comparison group validity of demographics and chronic disease status. CKD patients (eGFR < 60 mL/min/1.73 m2) performed worse than control groups (eGFR ≥ 60 mL/min/1.73 m2) on Orientation & Attention (SMD -0.79, 95% CI, -1.44 to -0.13), Language (SMD -0.63, 95% CI, -0.85 to -0.41), Concept Formation & Reasoning (SMD -0.63, 95% CI, -1.07 to -0.18), Executive Function (SMD -0.53, 95% CI, -0.85 to -0.21), Memory (SMD -0.48, 95% CI, -0.79 to -0.18), and Global Cognition (SMD -0.48, 95% CI, -0.72 to -0.24). Construction & Motor Praxis and Perception were unaffected (SMD -0.29, 95% CI, -0.90 to 0.32; SMD -1.12, 95% CI, -4.35 to 2.12). Language scores dropped with eGFR (<45 mL/min/1.73 m2 SMD -0.86, 95% CI, -1.25 to -46; 30 mL/min/1.73 m2 SMD -1.56, 95% CI, -2.27 to -0.84). Differences in Orientation & Attention were greatest at eGFR < 45 mL/min/1.73 m2 (SMD -4.62, 95% CI, -4.68 to -4.55). Concept Formation & Reasoning differences were greatest at eGFR < 45 mL/min/1.73 m2 (SMD -4.27, 95% CI, -4.23 to -4.27). Differences in Executive Functions were greatest at eGFR < 30 mL/min/1.73 m2 (SMD -0.54, 95% CI, -1.00 to -0.08). CONCLUSIONS: Cognitive changes occur early in CKD, and skills decline at different rates. Orientation & Attention and Language are particularly affected. The cognitive impact of CKD is likely to diminish patients' capacity to engage with healthcare decisions. An individual's cognitive trajectory may deviate from average.

Prognostic value of blood interleukin-6 in the prediction of functional outcome after stroke: a systematic review and meta-analysis.

We aimed to quantify the association of blood interleukin-6 (IL-6) concentrations with poor outcome after stroke and its added predictive value over clinical information. Meta-analysis of 24 studies confirmed this association with a weighted mean difference of 3.443 (1.592-5.294) pg/mL, despite high heterogeneity and publication bias. Individual participant data including 4112 stroke patients showed standardized IL-6 levels in the 4th quartile were independently associated with poor outcome (OR=2.346 (1.814-3.033), p<0.0001). However, the additional predictive value of IL-6 was moderate (IDI=1.5%, NRI=5.35%). Overall these results indicate an unlikely translation of IL-6 into clinical practice for this purpose.

Strokes: mimics and chameleons.

Diagnosing stroke is not always straightforward. Stroke mimics such as Todd's paresis or hemiplegic migraine account for between a fifth and a quarter of suspected strokes (depending on the setting in which they are assessed). Stroke chameleons can arise when the tempo of symptom onset is not apoplectic or if the loss of function is not clearly consistent with a deficit within an arterial territory. Thrombolysis and secondary prevention have much to offer patients with stroke chameleons, though those with stroke mimics may be harmed by these treatments and have more to gain from other therapies.

The Brazilian Family Health Program and secondary stroke and myocardial infarction prevention: a 6-year cohort study.

OBJECTIVES: We compared the incidence of recurrent or fatal cardiovascular disease in patients using Brazil's government-run Family Health Program (FHP) with those using non-FHP models of care. METHODS: From 2005 to 2010, we followed outpatients discharged from city public hospitals after a first ever stroke for stroke recurrence and myocardial infarction, using data from all city hospitals, death certificates, and outpatient monitoring in state-run and private units. RESULTS: In the follow-up period, 103 patients in the FHP units and 138 in the non-FHP units had exclusively state-run care. Stroke or myocardial infarction occurred in 30.1% of patients in the FHP group and 36.2% of patients in non-FHP care (rate ratio [RR] = 0.85; 95% confidence interval [CI] = 0.61, 1.18; P = .39); 37.9% of patients in FHP care and 54.3% in non-FHP care (RR = 0.68; 95% CI = 0.50, 0.92; P = .01) died. FHP use was associated with lower hazard of death from all causes (hazard ratio [HR] = 0.58; P = .005) after adjusting for age and stroke severity. The absolute risk reduction for death by all causes was 16.4%. CONCLUSIONS: FHP care is more effective than is non-FHP care at preventing death from secondary stroke and myocardial infarction.

The use of blood biomarkers to predict poor outcome after acute transient ischemic attack or ischemic stroke.

BACKGROUND AND PURPOSE: The prediction of death or disability ("poor outcome") after stroke by validated clinical models might be improved by the addition of blood biomarker measurements. We investigated whether such measurements improved the classification of patients into 4 categories of predicted risk of poor outcome: very high, intermediate high, intermediate low, and very low. METHODS: We prospectively recruited symptomatic patients within 24 hours of ischemic cerebrovascular events. We measured clinical prognostic variables in each patient. We drew blood soon after admission and measured markers of inflammation, thrombosis, cardiac strain, and cerebral damage. We assessed poor outcome at 3 months with the modified Rankin Scale and recovery of symptoms at 24 hours. We measured the association between blood marker levels and poor outcome after adjustment for stroke severity and age with multivariate logistic regression. Where these associations were statistically significant, we calculated the net reclassification index. RESULTS: We recruited 270 patients with acute ischemic cerebrovascular events. At 3 months, 112 patients had a poor outcome. After adjustment for stroke severity and age, only interleukin-6 and N-terminal pro-brain natriuretic peptide were significantly associated with poor outcome. The addition of either interleukin-6 or N-terminal pro-brain natriuretic peptide to National Institutes of Health Stroke Scale and age did not improve the prediction of a poor outcome. CONCLUSIONS: Neither interleukin-6 nor N-terminal pro-brain natriuretic peptide had sufficient predictive power to be of clinical use to predict poor outcome after stroke. The search for better markers to improve the classification of patients across clinically relevant boundaries of predicted probabilities of outcome events needs to continue.

The use of LiDCO based fluid management in patients undergoing hip fracture surgery under spinal anaesthesia: neck of femur optimisation therapy - targeted stroke volume (NOTTS): study protocol for a randomized controlled trial.

BACKGROUND: Approximately 70,000 patients/year undergo surgery for repair of a fractured hip in the United Kingdom. This is associated with 30-day mortality of 9% and survivors have a considerable length of acute hospital stay postoperatively (median 26 days). Use of oesophageal Doppler monitoring to guide intra-operative fluid administration in hip fracture repair has previously been associated with a reduction in hospital stay of 4-5 days. Most hip fracture surgery is now performed under spinal anaesthesia. Oesophageal Doppler monitoring may be unreliable in the presence of spinal anaesthesia and most patients would not tolerate the probes. An alternative method of guiding fluid administration (minimally-invasive arterial pulse contour analysis) has been shown to reduce length of stay in high-risk surgical patients but has never been studied in hip fracture surgery. METHODS: Single-centre randomised controlled parallel group trial. Randomisation by website using computer generated concealed tables. SETTING: University hospital in UK. PARTICIPANTS: 128 patients with acute primary hip fracture listed for operative repair under spinal anaesthesia and aged > 65 years. INTERVENTION: Stroke volume guided intra-operative fluid management. Continuous measurement of SV recorded by a calibrated cardiac output monitor (LiDCOplus). Maintenance fluid and 250 ml colloid boluses given to achieve sustained 10% increases in stroke volume. CONTROL GROUP: fluid administration at the responsible (blinded) anaesthetist's discretion. The intervention terminates at the end of the surgical procedure and post-operative fluid management is at the responsible anaesthetist's discretion. PRIMARY OUTCOME: length of acute hospital stay is determined by a blinded team of clinicians. Secondary outcomes include number of complications and total cost of care. Funding NIHR/RfPB: PB-PG-0407-13073. TRIAL REGISTRATION: Current Controlled Trials ISRCTN88284896.

Association of circulating inflammatory markers with recurrent vascular events after stroke: a prospective cohort study.

BACKGROUND AND PURPOSE: inflammatory markers may be associated with recurrent vascular events after stroke. We aimed to determine the association between IL-6, C-reactive protein, fibrinogen and white cell count, with recurrent vascular events after stroke, and to compare the association between circulating inflammatory markers with the risk of death from vascular vs nonvascular causes. METHODS: we prospectively recruited patients with acute stroke (n=817) and followed them for up to 4 years for the occurrence of fatal or nonfatal recurrent stroke, myocardial infarction or fatal vascular events, and death from any cause (n=159). RESULTS: the delay to assessment was a median of 10 days. The adjusted incidence of the outcome cluster recurrent stroke, myocardial infarction or vascular death after stroke was significantly higher with higher levels of IL-6 (75(th) to 25(th) percentile hazard ratio, 1.56; 95% CI, 1.37-1.77), C-reactive protein (75(th) to 25(th) percentile hazard ratio, 1.08; 95% CI, 1.04-1.11), and fibrinogen (75(th) to 25(th) percentile hazard ratio, 1.45; 95% CI, 1.24-1.72). The associations between inflammatory markers and death were stronger than with recurrent vascular events. The associations of inflammatory markers with vascular and nonvascular deaths were similar. CONCLUSIONS: although inflammatory markers were associated with an increased risk of recurrent vascular events and vascular death after stroke, they were also associated with nonvascular causes of death, suggesting that inflammatory markers do not play a causal role specifically in the generation of recurrent vascular events after stroke. Future studies of the prediction of recurrent vascular events after stroke should concentrate on clinical variables or different blood markers.

Inflammatory markers and poor outcome after stroke: a prospective cohort study and systematic review of interleukin-6.

BACKGROUND: The objective of this study was to determine whether: (a) markers of acute inflammation (white cell count, glucose, interleukin-6, C-reactive protein, and fibrinogen) are associated with poor outcome after stroke and (b) the addition of markers to previously validated prognostic models improves prediction of poor outcome. METHODS AND FINDINGS: We prospectively recruited patients between 2002 and 2005. Clinicians assessed patients and drew blood for inflammatory markers. Patients were followed up by postal questionnaire for poor outcome (a score of>2 on the modified Rankin Scale) and death through the General Register Office (Scotland) at 6 mo. We performed a systematic review of the literature and meta-analysis of the association between interleukin-6 and poor outcome after stroke to place our study in the context of previous research. We recruited 844 patients; mortality data were available in 844 (100%) and functional outcome in 750 (89%). After appropriate adjustment, the odds ratios for the association of markers and poor outcome (comparing the upper and the lower third) were interleukin-6, 3.1 (95% CI: 1.9-5.0); C-reactive protein, 1.9 (95% CI: 1.2-3.1); fibrinogen, 1.5 (95% CI: 1.0-2.36); white cell count, 2.1 (95% CI: 1.3-3.4); and glucose 1.3 (95% CI: 0.8-2.1). The results for interleukin-6 were similar to other studies. However, the addition of inflammatory marker levels to validated prognostic models did not materially improve model discrimination, calibration, or reclassification for prediction of poor outcome after stroke. CONCLUSIONS: Raised levels of markers of the acute inflammatory response after stroke are associated with poor outcomes. However, the addition of these markers to a previously validated stroke prognostic model did not improve the prediction of poor outcome. Whether inflammatory markers are useful in prediction of recurrent stroke or other vascular events is a separate question, which requires further study. Please see later in the article for the Editors' Summary.

Incidental findings on brain magnetic resonance imaging: systematic review and meta-analysis.

OBJECTIVE: To quantify the prevalence of incidental findings on magnetic resonance imaging (MRI) of the brain. DESIGN: Systematic review and meta-analysis of observational studies. DATA SOURCES: Ovid Medline (1950 to May 2008), Embase (1980 to May 2008), and bibliographies of relevant articles. Review methods Two reviewers sought and assessed studies of people without neurological symptoms who underwent MRI of the brain with or without intravenous contrast for research purposes or for occupational, clinical, or commercial screening. MAIN OUTCOME MEASURES: Overall disease specific and age specific prevalence of incidental brain findings, calculated by meta-analysis of pooled proportions using DerSimonian-Laird weights in a random effects model. RESULTS: In 16 studies, 135 of 19 559 people had neoplastic incidental brain findings (prevalence 0.70%, 95% confidence interval 0.47% to 0.98%), and prevalence increased with age (chi(2) for linear trend, P=0.003). In 15 studies, 375 of 15 559 people had non-neoplastic incidental brain findings (prevalence 2.0%, 1.1% to 3.1%, excluding white matter hyperintensities, silent infarcts, and microbleeds). The number of asymptomatic people needed to scan to detect any incidental brain finding was 37. The prevalence of incidental brain findings was higher in studies using high resolution MRI sequences than in those using standard resolution sequences (4.3% v 1.7%, P<0.001). The prevalence of neoplastic incidental brain findings increased with age. CONCLUSIONS: Incidental findings on brain MRI are common, prevalence increases with age, and detection is more likely using high resolution MRI sequences than standard resolution sequences. These findings deserve to be mentioned when obtaining informed consent for brain MRI in research and clinical practice but are not sufficient to justify screening healthy asymptomatic people.

Screening using whole-body magnetic resonance imaging scanning: who wants an incidentaloma?

OBJECTIVE: Some private health screening companies in the UK provide 'health check-ups' using whole-body magnetic resonance imaging (MRI), in spite of the lack of evidence demonstrating that such screening is worthwhile. We discuss the issues surrounding the use of an MRI scan as a screening test in 'health check-ups' and set out our concerns. CONCLUSION: Because of the five balance between the potential perils and benefits of the unselective use of brain MRI for 'health check-ups', its use should be restricted to a research setting.