Observer reliability of CT angiography in the assessment of acute ischaemic stroke: data from the Third International Stroke Trial.

INTRODUCTION: CT angiography (CTA) is often used for assessing patients with acute ischaemic stroke. Only limited observer reliability data exist. We tested inter- and intra-observer reliability for the assessment of CTA in acute ischaemic stroke. METHODS: We selected 15 cases from the Third International Stroke Trial (IST-3, ISRCTN25765518) with various degrees of arterial obstruction in different intracranial locations on CTA. To assess inter-observer reliability, seven members of the IST-3 expert image reading panel (>5 years experience reading CTA) and seven radiology trainees (<2 years experience) rated all 15 scans independently and blind to clinical data for: presence (versus absence) of any intracranial arterial abnormality (stenosis or occlusion), severity of arterial abnormality using relevant scales (IST-3 angiography score, Thrombolysis in Cerebral Infarction (TICI) score, Clot Burden Score), collateral supply and visibility of a perfusion defect on CTA source images (CTA-SI). Intra-observer reliability was assessed using independently repeated expert panel scan ratings. We assessed observer agreement with Krippendorff's-alpha (K-alpha). RESULTS: Among experienced observers, inter-observer agreement was substantial for the identification of any angiographic abnormality (K-alpha = 0.70) and with an angiography assessment scale (K-alpha = 0.60-0.66). There was less agreement for grades of collateral supply (K-alpha = 0.56) or for identification of a perfusion defect on CTA-SI (K-alpha = 0.32). Radiology trainees performed as well as expert readers when additional training was undertaken (neuroradiology specialist trainees). Intra-observer agreement among experts provided similar results (K-alpha = 0.33-0.72). CONCLUSION: For most imaging characteristics assessed, CTA has moderate to substantial observer agreement in acute ischaemic stroke. Experienced readers and those with specialist training perform best.

Computed tomography angiography or magnetic resonance angiography for detection of intracranial vascular malformations in patients with intracerebral haemorrhage.

BACKGROUND: Intracranial vascular malformations (brain or pial/dural arteriovenous malformations/fistulae, and aneurysms) are the leading cause of intracerebral haemorrhage (ICH) in young adults. Early identification of the intracranial vascular malformation may improve outcome if treatment can prevent ICH recurrence. Catheter intra-arterial digital subtraction angiography (IADSA) is considered the reference standard for the detection an intracranial vascular malformation as the cause of ICH. Computed tomography angiography (CTA) and magnetic resonance angiography (MRA) are less invasive than IADSA and may be as accurate for identifying some causes of ICH. OBJECTIVES: To evaluate the diagnostic test accuracy of CTA and MRA versus IADSA for the detection of intracranial vascular malformations as a cause of ICH. SEARCH METHODS: We searched MEDLINE (1948 to August 2013), EMBASE (1980 to August 2013), MEDION (August 2013), the Database of Abstracts of Reviews of Effects (DARE; August 2013), the Health Technology Assessment Database (HTA; August 2013), ClinicalTrials.gov (August 2013), and WHO ICTRP (International Clinical Trials Register Portfolio; August 2013). We also performed a cited reference search for forward tracking of relevant articles on Google Scholar (http://scholar.google.com/), screened bibliographies, and contacted authors to identify additional studies. SELECTION CRITERIA: We selected studies reporting data that could be used to construct contingency tables that compared CTA or MRA, or both, with IADSA in the same patients for the detection of intracranial vascular malformations following ICH. DATA COLLECTION AND ANALYSIS: Two authors (CBJ and RA-SS) independently extracted data on study characteristics and measures of test accuracy. Two authors (CBJ and PMW) independently extracted data on test characteristics. We obtained data restricted to the subgroup undergoing IADSA in studies using multiple reference standards. We combined data using the bivariate model. We generated forest plots of the sensitivity and specificity of CTA and MRA and created a summary receiver operating characteristic plot. MAIN RESULTS: Eleven studies (n = 927 participants) met our inclusion criteria. Eight studies compared CTA with IADSA (n = 526) and three studies compared MRA with IADSA (n = 401). Methodological quality varied considerably among studies, with partial verification bias in 7/11 (64%) and retrospective designs in 5/10 (50%). In studies of CTA, the pooled estimate of sensitivity was 0.95 (95% confidence interval (CI) 0.90 to 0.97) and specificity was 0.99 (95% CI 0.95 to 1.00). The results remained robust in a sensitivity analysis in which only studies evaluating adult patients (≥ 16 years of age) were included. In studies of MRA, the pooled estimate of sensitivity was 0.98 (95% CI 0.80 to 1.00) and specificity was 0.99 (95% CI 0.97 to 1.00). An indirect comparison of CTA and MRA using a bivariate model incorporating test type as one of the parameters failed to reveal a statistically significant difference in sensitivity or specificity between the two imaging modalities (P value = 0.6). AUTHORS' CONCLUSIONS: CTA and MRA appear to have good sensitivity and specificity following ICH for the detection of intracranial vascular malformations, although several of the included studies had methodological shortcomings (retrospective designs and partial verification bias in particular) that may have increased apparent test accuracy.

Future trials of endovascular mechanical recanalisation therapy in acute ischemic stroke patients: a position paper endorsed by ESMINT and ESNR : part I: Current situation and major research questions.

A new era of stroke treatment may have begun with mechanical thrombectomy (MT) by fully deployed closed-cell self-expanding stents (stent-triever). Multiple case series and the first randomised controlled trials (RCTs) have now been published. More studies are under way involving large numbers of patients, which in turn has resulted in less strict "pragmatic" study protocols. Problems with current trials include a lack of standardisation in the conduct of the recanalisation procedure, the definition of primary endpoints such as the grade of arterial recanalisation and tissue reperfusion, and the post-surgical care provided. In Part 1 of this two part series, we outline the current situation and the major research questions.

Future trials of endovascular mechanical recanalisation therapy in acute ischemic stroke patients - a position paper endorsed by ESMINT and ESNR : part II: methodology of future trials.

Based on current data and experience, the joint working group of the European Society of Minimally Invasive Neurological Therapy (ESMINT) and the European Society of Neuroradiology (ESNR) make suggestions on trial design and conduct aimed to investigate therapeutic effects of mechanical thrombectomy (MT). We anticipate that this roadmap will facilitate the setting up and conduct of successful trials in close collaboration with our neighbouring disciplines.

Research governance impediments to clinical trials: a retrospective survey.

OBJECTIVE: We sought to evaluate the delays, between-centre variations in practice, and opportunity costs attributable to delays in research governance approval of clinical trials in the United Kingdom. DESIGN: Retrospective survey. SETTING: Research and Development (R&D) departments at 50 UK National Health Service hospital trusts governing 57 hospital sites. PARTICIPANTS: R&D departments participating in four randomized multicentre clinical trials coordinated by our Neurosciences Trials Unit. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Median delay between application and research governance approval. RESULTS: Only half of the R&D departments used the UK online R&D form. Only a single copy of the application was required by 96% of R&D departments. The median delay between application and research governance approval was 44 working days (inter-quartile range 23-80). A delay of >20 working days was incurred by 43 applications (75%), of which 24 (56%) were not explicable and 11 (20%) were attributable to local funding negotiations. Based on the trial randomization rates at each centre, 108 patients (17% of all patients randomized) could have been randomized during the delay, at a crude cost to funding agencies of 53,743 pounds; if a four week delay was deemed acceptable, 75 patients (12% of all patients randomized) could have been randomized during unacceptable delays, at a crude cost to funding agencies of 37,700 pounds. CONCLUSIONS: The UK research governance system incurs unacceptably long and costly delays for clinical trials. Urgent reform is needed, including rapid design and uniform implementation of the 'bureaucracy busting' measures in Best Research for Best Health.

Open access neuroimaging for general practitioners--diagnostic yield and influence on patient management.

This study assessed the first year of a regional general practitioner (GP) open-access neuroimaging service, to determine diagnostic yield and influence on patient management. Overall, 48.1% of examinations demonstrated a radiologically significant abnormality with 64.1% of spinal imaging examinations demonstrating significant findings. Utilised appropriately, a regional open-access neuroimaging service has good diagnostic yield and may influence the management of most referred patients.