Elevated C-reactive protein increases diagnostic accuracy of algorithm-defined Stroke Associated Pneumonia in afebrile patients

Background and aim: Pyrexia dependent clinical algorithms may under or over diagnose Stroke Associated Pneumonia (SAP). This study investigates whether inclusion of elevated C-reactive protein (CRP) as a criterion improves diagnosis. Methods: The contribution of CRP ≥30 mg/L as an additional criterion to a Centres for Disease Control and Prevention (CDC) based algorithm incorporating pyrexia with chest signs and leucocytosis and/or chest infiltrates to diagnose SAP was assessed in 1088 acute stroke patients from 37 UK stroke units. The sensitivity, specificity and positive predictive value of different approaches were assessed using adjudicated SAP as the reference standard.Results: Adding elevated CRP to all algorithm criteria did not increase diagnostic accuracy compared with the algorithm alone against adjudicated SAP (sensitivity 0.74 [95% CI 0.65-0.81] v 0.72 [95% CI 0.64-0.80], specificity 0.97 [95% CI 0.96-0.98] for both; kappa (0·70 [95% C.I. 0.63-0.77] for both). In afebrile patients (n=965), elevated CRP with chest and laboratory findings had sensitivity of 0.84 [95% CI 0.67-0.93], specificity of 0.99 [95% CI 0.98-1.00] and kappa 0·80 [95% C.I. 0.70-0.90]). The modified algorithm of pyrexia or elevated CRP and chest signs with infiltrates or leucocytosis had sensitivity of 0.94 [95% CI 0.87-0.97], specificity of 0.96 [95% CI 0.94-0.97] and kappa of 0.88 [95% C.I. 0.84-0.93]) against adjudicated SAP.Conclusions: An algorithm consisting of pyrexia or CRP ≥30 mg/L, positive chest signs, leucocytosis and/or chest infiltrates has high accuracy and can be used to standardise SAP diagnosis in clinical or research settings

Cerebral microbleeds and intracranial haemorrhage risk in patients anticoagulated for atrial fibrillation after acute ischaemic stroke or transient ischaemic attack (CROMIS-2):a multicentre observational cohort study

Background: Cerebral microbleeds are a potential neuroimaging biomarker of cerebral small vessel diseases that are prone to intracranial bleeding. We aimed to determine whether presence of cerebral microbleeds can identify patients at high risk of symptomatic intracranial haemorrhage when anticoagulated for atrial fibrillation after recent ischaemic stroke or transient ischaemic attack. Methods: Our observational, multicentre, prospective inception cohort study recruited adults aged 18 years or older from 79 hospitals in the UK and one in the Netherlands with atrial fibrillation and recent acute ischaemic stroke or transient ischaemic attack, treated with a vitamin K antagonist or direct oral anticoagulant, and followed up for 24 months using general practitioner and patient postal questionnaires, telephone interviews, hospital visits, and National Health Service digital data on hospital admissions or death. We excluded patients if they could not undergo MRI, had a definite contraindication to anticoagulation, or had previously received therapeutic anticoagulation. The primary outcome was symptomatic intracranial haemorrhage occurring at any time before the final follow-up at 24 months. The log-rank test was used to compare rates of intracranial haemorrhage between those with and without cerebral microbleeds. We developed two prediction models using Cox regression: first, including all predictors associated with intracranial haemorrhage at the 20% level in univariable analysis; and second, including cerebral microbleed presence and HAS-BLED score. We then compared these with the HAS-BLED score alone. This study is registered with ClinicalTrials.gov, number NCT02513316. Findings: Between Aug 4, 2011, and July 31, 2015, we recruited 1490 participants of whom follow-up data were available for 1447 (97%), over a mean period of 850 days (SD 373; 3366 patient-years). The symptomatic intracranial haemorrhage rate in patients with cerebral microbleeds was 9·8 per 1000 patient-years (95% CI 4·0–20·3) compared with 2·6 per 1000 patient-years (95% CI 1·1–5·4) in those without cerebral microbleeds (adjusted hazard ratio 3·67, 95% CI 1·27–10·60). Compared with the HAS-BLED score alone (C-index 0·41, 95% CI 0·29–0·53), models including cerebral microbleeds and HAS-BLED (0·66, 0·53–0·80) and cerebral microbleeds, diabetes, anticoagulant type, and HAS-BLED (0·74, 0·60–0·88) predicted symptomatic intracranial haemorrhage significantly better (difference in C-index 0·25, 95% CI 0·07–0·43, p=0·0065; and 0·33, 0·14–0·51, p=0·00059, respectively). Interpretation: In patients with atrial fibrillation anticoagulated after recent ischaemic stroke or transient ischaemic attack, cerebral microbleed presence is independently associated with symptomatic intracranial haemorrhage risk and could be used to inform anticoagulation decisions. Large-scale collaborative observational cohort analyses are needed to refine and validate intracranial haemorrhage risk scores incorporating cerebral microbleeds to identify patients at risk of net harm from oral anticoagulation. Funding: The Stroke Association and the British Heart Foundation

Baseline factors associated with early and late death in intracerebral haemorrhage survivors

Background and purpose: The aim of this study was to determine whether early and late death are associated with different baseline factors in intracerebral haemorrhage (ICH) survivors. Methods: This was a secondary analysis of the multicentre prospective observational CROMIS‐2 ICH study. Death was defined as ‘early’ if occurring within 6 months of study entry and ‘late’ if occurring after this time point. Results: In our cohort (n = 1094), there were 306 deaths (per 100 patient‐years: absolute event rate, 11.7; 95% confidence intervals, 10.5–13.1); 156 were ‘early’ and 150 ‘late’. In multivariable analyses, early death was independently associated with age [per year increase; hazard ratio (HR), 1.05, P = 0.003], history of hypertension (HR, 1.89, P = 0.038), pre‐event modified Rankin scale score (per point increase; HR, 1.41, P < 0.0001), admission National Institutes of Health Stroke Scale score (per point increase; HR, 1.11, P < 0.0001) and haemorrhage volume >60 mL (HR, 4.08, P < 0.0001). Late death showed independent associations with age (per year increase; HR, 1.04, P = 0.003), pre‐event modified Rankin scale score (per point increase; HR, 1.42, P = 0.001), prior anticoagulant use (HR, 2.13, P = 0.028) and the presence of intraventricular extension (HR, 1.73, P = 0.033) in multivariable analyses. In further analyses where time was treated as continuous (rather than dichotomized), the HR of previous cerebral ischaemic events increased with time, whereas HRs for Glasgow Coma Scale score, National Institutes of Health Stroke Scale score and ICH volume decreased over time. Conclusions: We provide new evidence that not all baseline factors associated with early mortality after ICH are associated with mortality after 6 months and that the effects of baseline variables change over time. Our findings could help design better prognostic scores for later death after ICH

Cerebral microbleeds and intracranial haemorrhage risk in patients anticoagulated for atrial fibrillation after acute ischaemic stroke or transient ischaemic attack (CROMIS-2): a multicentre observational cohort study

Summary Background: Cerebral microbleeds are a potential neuroimaging biomarker of cerebral small vessel diseases that are prone to intracranial bleeding. We aimed to determine whether presence of cerebral microbleeds can identify patients at high risk of symptomatic intracranial haemorrhage when anticoagulated for atrial fibrillation after recent ischaemic stroke or transient ischaemic attack. Methods: Our observational, multicentre, prospective inception cohort study recruited adults aged 18 years or older from 79 hospitals in the UK and one in the Netherlands with atrial fibrillation and recent acute ischaemic stroke or transient ischaemic attack, treated with a vitamin K antagonist or direct oral anticoagulant, and followed up for 24 months using general practitioner and patient postal questionnaires, telephone interviews, hospital visits, and National Health Service digital data on hospital admissions or death. We excluded patients if they could not undergo MRI, had a definite contraindication to anticoagulation, or had previously received therapeutic anticoagulation. The primary outcome was symptomatic intracranial haemorrhage occurring at any time before the final follow-up at 24 months. The log-rank test was used to compare rates of intracranial haemorrhage between those with and without cerebral microbleeds. We developed two prediction models using Cox regression: first, including all predictors associated with intracranial haemorrhage at the 20% level in univariable analysis; and second, including cerebral microbleed presence and HAS-BLED score. We then compared these with the HAS-BLED score alone. This study is registered with ClinicalTrials.gov, number NCT02513316. Findings: Between Aug 4, 2011, and July 31, 2015, we recruited 1490 participants of whom follow-up data were available for 1447 (97%), over a mean period of 850 days (SD 373; 3366 patient-years). The symptomatic intracranial haemorrhage rate in patients with cerebral microbleeds was 9·8 per 1000 patient-years (95% CI 4·0–20·3) compared with 2·6 per 1000 patient-years (95% CI 1·1–5·4) in those without cerebral microbleeds (adjusted hazard ratio 3·67, 95% CI 1·27–10·60). Compared with the HAS-BLED score alone (C-index 0·41, 95% CI 0·29–0·53), models including cerebral microbleeds and HAS-BLED (0·66, 0·53–0·80) and cerebral microbleeds, diabetes, anticoagulant type, and HAS-BLED (0·74, 0·60–0·88) predicted symptomatic intracranial haemorrhage significantly better (difference in C-index 0·25, 95% CI 0·07–0·43, p=0·0065; and 0·33, 0·14–0·51, p=0·00059, respectively). Interpretation In patients with atrial fibrillation anticoagulated after recent ischaemic stroke or transient ischaemic attack, cerebral microbleed presence is independently associated with symptomatic intracranial haemorrhage risk and could be used to inform anticoagulation decisions. Large-scale collaborative observational cohort analyses are needed to refine and validate intracranial haemorrhage risk scores incorporating cerebral microbleeds to identify patients at risk of net harm from oral anticoagulation. Funding The Stroke Association and the British Heart Foundation

Abstract 3463: Physicians’ Knowledge of Driving Limitation Following Stroke or TIA is Inadequate

Background: An increasing number of TIA and minor stroke patients are assessed and discharged by front-line staff in emergency or acute assessment units. As capacity to drive is affected by a stroke or TIA, we assessed the level of knowledge of driving restrictions after stroke or TIA in frontline doctors. Method: A structured multiple choice questionnaire was used to assess knowledge of driving restrictions after stroke in 195 doctors involved in assessing patients in the Emergency Department or acute assessment units. The questionnaire took between 10-15 minutes to complete and tested knowledge of driving restrictions after minor stroke or TIA for those holding a domestic (Group 1) or a commercial (Group 2) licence. The wording of the questions was similar to that used in statutory medical guidance by the Licensing Authority. Results: The 195 doctors included 8 consultants, 88 senior residents, 22 junior residents and 77 foundation level trainees. Only 43 (23%) doctors had been specifically instructed about driving restrictions in stroke; 89 (45%) had received no formal education on driving restrictions following medical illnesses. The majority (155, 86%) were aware that it was patients’ responsibility to inform the licensing agency of driving restrictions due to medical illnesses. Only 72 (37%) and 84 (43%) doctors correctly identified that TIA patients were not allowed to drive for 1 month if holding a domestic licence and for 1 year if holding a commercial licence respectively. Forty eight (25%) believed that no restrictions applied after a TIA. Driving restrictions for stroke with complete recovery of 1 month for domestic and 1 year for commercial license were correctly answered by 56 (29%) and 117 (71%); only 23 (12%) thought that no restrictions applied. There were no significant variations in knowledge attributable to seniority, formal instruction of driving regulations or working with stroke patients. Conclusions: Doctors have limited knowledge of driving restrictions after TIA or minor stroke, which presents significant public safety and medico-legal risks. Innovative methods are required to improve the acquisition and retention this knowledge in front line doctors. </jats:p

Abstract T MP84: Early Specialist Management of In-Hospital Stroke Patients

Background and Objectives: In-hospital stroke (IHS) is associated with high mortality and disability but management is delayed compared with out of hospital stroke presenting to emergency rooms. The hypothesis prior to data collection was that early referral and specialist management of IHS patients will be associated with lower mortality and better functional outcomes at 90 days. Methods: Pre-specified analysis of prospective registry data of consecutive hospitalised stroke patients between January 2009 and December 2010 fulfilling the criteria: 1) admission to hospital with a non-stroke diagnosis; 2) onset of new neurological deficits after admission; 3) CT/MRI confirmation of new ischaemic or haemorrhagic changes. Intervention: Early referral and specialist management of IHS within 3 hours of symptom onset versus late referral after 3 hours. Specialist management consisted of neurological assessment, thrombolysis if appropriate, vascular investigations, anti-thrombotic treatment and transfer to stroke unit for physiological optimisation and prevention of complications. Main Outcomes: Blinded assessment of d ichotomised modified Rankin Scale (mRS) score of 0-2 and all-cause mortality at 90 days. All patients completed 90 day follow up. Results: Eighty four (4.6%) of 1836 stroke patients had IHS (mean age 74 years; 51% male), of whom 78 were ischaemic and 6 haemorrhagic. There were no significant differences in baseline characteristics between 53 (63%) early and 31 (37%) late referrals. Thrombolysis was performed in 29 of the 37/78 (47%) potentially eligible patients. Early specialist management improved functional outcomes (mRS 0-2 at 90 days 40% v 7%, p=0.001) but not all-cause mortality (32% v 37%, p=0.74). Early specialist management was an independent predictor of mRS 0-2 at 90 days [OR 1.13 (95% C.I. = 1.10-1.27), p=0.002] after adjusting for age, cause for hospital admission, stroke severity and thrombolysis. Conclusions: Early referral and specialist management of IHS patients improved functional outcomes but did not reduce mortality at 90 days, independent of thrombolysis. Further studies are needed to confirm its benefit in wider clinical practice. </jats:p

The Impact of Early Specialist Management on Outcomes of Patients with In-Hospital Stroke

Delays in treatment of in-hospital stroke (IHS) adversely affect patient outcomes. We hypothesised that early referral and specialist management of IHS patients will improve outcomes at 90 days. Baseline characteristics, assessment delays, thrombolysis eligibility, 90-day functional outcomes and all-cause mortality were compared between IHS patients referred for specialist stroke management within 3 hours of symptom onset (early referrals) and later referrals. Patients were identified from a prospective stroke registry between January 2009 and December 2010. Inclusion criteria were primary admission with a non-stroke diagnosis, onset of new neurological deficits after admission and early ischaemic changes on CT or MR imaging. Eighty four (4.6%) of 1836 stroke patients had IHS (mean age 74 year; 51% male, median NIHSS score 10). There were no significant differences in baseline characteristics between 53 (63%) early and 31 (37%) late referrals. Thrombolysis was performed in 29 (76%) of the 37/78 (47%) potentially eligible patients; 7 patients were excluded because specialist referral was delayed beyond 4.5 hours despite symptom recognition within 3 hours of onset. Early referral improved functional outcomes (modified Rankin Scale 0-2 at 90 days 40% v 7%, p = 0.001) and was an independent predictor of mRS 0-2 at 90 days after adjusting for age, pre-morbid function, primary cause for hospital admission and stroke severity [OR 1.13 (95% C.I. = 1.10-1.27), p = 0.002]. Early referral and specialist management of IHS patients that includes thrombolysis is associated with better functional outcomes at 90 days.</p

Abstract 56: Thrombolysis in Selected Patients with Wake Up Stroke is Feasible with Similar Safety as Thrombolysis in 0-4.5 Hours

Introduction Thrombolysis with alteplase is effective within 4.5 hours of ischaemic stroke onset in patients with no or early ischaemic changes (EIC) on CT. Patients with wake up strokes (WUS) make up to 25' of all strokes but are excluded on the basis of time alone. Emerging data suggest that imaging appearances in many WUS patients are similar to those treated within 4.5 h and recanalisation therapies may be beneficial. Hypothesis Treatment with alteplase in WUS patients selected on CT imaging findings showing no or limited EIC who would otherwise be eligible for thrombolysis will have functional outcome and bleeding risks similar to those thrombolysed within 4.5 hours of stroke onset. Methods We analysed registry data between January 2009 and December 2010 for WUS patients thrombolysed on compassionate grounds with consent and compared their outcomes with those thrombolysed within 4.5 hours of stroke onset. Standard guidelines were followed but there was no upper age limit for thrombolysis. WUS patients were thrombolysed if they met all eligibility criteria apart from time and the non-enhanced CT scan showed an Alberta Stroke Program Early CT Score (ASPECTS) of ≥7. CT Perfusion (CTP) mismatch was used as an additional modality for assessing eligibility for thrombolysis in a proportion of WUS patients but was not obligatory. Inclusion criteria for the analysis were defined a priori and were masked to outcomes. Results The analysis included 356 patients thrombolysed within 4.5 hours of stroke onset and 68 thrombolysed WUS patients. The two groups were comparable for mean age (72.6 v 74.8, years, p=0.28) and vascular risks profile but there were more women in the WUS group (66% v 52%, p=0.034). There were fewer WUS patients with premorbid Rankin Score (mRS) of 0-2 (69% v 84% p=0.01). There were no differences in mean baseline BP (151/85 v 153/84 mm Hg, p=0.55), mean blood glucose (6.5 v 6.5 mmols/L, p=0.99) and mean National Institute of Health Stroke Scale (NIHSS) score (13.2 v 12.6, p=0.44). CTP was undertaken in 26% patients within 4.5 h and in 67% of WUS patients (p&lt;0.0001). The door to needle time was 59 minutes and 73 minutes respectively (p=0.11). There were no differences in mean NIHSS score at 24 hours (9.2 v 8.1, p=0.32), any intracranial haemorrhage (ICH) (17% v 22%, p=0.21), symptomatic ICH (2.5% v 2.9%, p=0.55) and mRS 0-2 at 3 months (49% v 37%, p=0.10) between patients within 4.5 h and WUS patients. Mortality at 3 months was lower in thrombolysed WUS patients (15% v 24%, p=0.063) and became significant after adjusting for co-variates in multiple regression (p=0.024). Conclusion Functional and safety outcomes after thrombolysis in WUS patients selected using CT imaging based protocols is comparable to that of patients treated within 4.5 h of stroke onset. Our experience suggests that randomization of patients with WUS on the basis of defined imaging criteria in thrombolysis trials is appropriate. </jats:p