The individual and combined impacts of pre-existing diabetes and dementia on ischemic stroke outcomes: a registry-based cohort study.

BACKGROUND: Individually, diabetes mellitus and dementia are associated with poorer outcomes after stroke. However, the combined impact of these pre-existing factors on acute ischemic stroke (AIS) outcomes has not been examined. METHODS: All consecutive patients with AIS admitted to Norfolk and Norwich University Hospitals between 2003 and 2016 (catchment population ~ 900,000) were divided into four groups: those with neither diabetes nor dementia (reference), with diabetes without dementia, with dementia without diabetes, and with both co-morbidities. In-hospital mortality, length of hospital stay (LoS), and disability outcomes were analysed using logistic regressions. Post-discharge mortality and recurrence were assessed using Cox regressions. Additionally, interaction terms were added to the models for the short-term outcomes and long-term mortality to test for synergistic effects of diabetes and dementia. Models were adjusted for age, sex, Oxfordshire Community Stroke Project classification, comorbidities, hematological and biochemical measures, and antithrombotic medications. RESULTS: The cohort was 10,812 patients with 52% females and a median age of 80. The median follow-up was 3.8 years for stroke recurrence and 5.5 years for mortality. No significant differences between the four groups existed for in-hospital mortality and post-stroke disability. Patients with dementia had significantly longer LoS (OR 2.25 [95% CI: 1.34-3.77] and 1.31 [1.02-1.68] with and without diabetes, respectively). Patients with both comorbidities had the highest risk of stroke recurrence (HR 2.06 [1.12-3.77]), followed by those with only dementia (1.59 [1.15-2.20]) and only diabetes (1.25 [1.06-1.49]). Similarly, the patient group with both diabetes and dementia had the highest long-term mortality risk (1.76 [1.33-2.37]). The hazard ratios for patients with only dementia and only diabetes were 1.71 [1.46-2.01] and 1.19 [1.08-1.32], respectively. No significant interactions were seen between diabetes and dementia with regards to their effects on the outcomes. CONCLUSION: Individual and cumulative impacts of the two conditions on long-term mortality and stroke recurrence were notable. However, no synergistic impact of the two comorbidities were seen on the stroke outcomes tested in our study. Therefore, tailoring the management of stroke patients based on additional requirements associated with each pre-existing condition will be more impactful towards improving outcomes.

Prevalence of orthostatic hypertension and its association with cerebrovascular diagnoses in patients with suspected TIA and minor stroke.

PURPOSE: We aimed to compare the rate of stroke, transient ischemic attack, and cerebrovascular disease diagnoses across groups of patients based on their orthostatic blood pressure response in a transients ischemic attack clinic setting. MATERIALS AND METHODS: We retrospectively analysed prospectively collected data from 3201 patients referred to a transient ischemic attack (TIA)/minor stroke outpatients clinic. Trained nurses measured supine and standing blood pressure using an automated blood pressure device and the patients were categorized based on their orthostatic blood pressure change into four groups: no orthostatic blood pressure rise, systolic orthostatic hypertension, diastolic orthostatic hypertension, and combined orthostatic hypertension. Then, four stroke physicians, who were unaware of patients' orthostatic BP response, assessed the patients and made diagnoses based on clinical and imaging data. We compared the rate of stroke, TIA, and cerebrovascular disease (either stroke or TIA) diagnoses across the study groups using Pearson's χ2 test. The effect of confounders was adjusted using a multivariate logistic regression analysis. RESULTS: Cerebrovascular disease was significantly less common in patients with combined systolic and diastolic orthostatic hypertension compared to the "no rise" group [OR = 0.56 (95% CI 0.35-0.89]. The odds were even lower among the subgroups of patients with obesity [OR = 0.31 (0.12-0.80)], without history of smoking [OR 0.34 (0.15-0.80)], and without hypertension [OR = 0.42 (95% CI 0.19-0.92)]. We found no significant relationship between orthostatic blood pressure rise with the diagnosis of stroke. However, the odds of TIA were significantly lower in patients with diastolic [OR 0.82 (0.68-0.98)] and combined types of orthostatic hypertension [OR = 0.54 (0.32-0.93)]; especially in patients younger than 65 years [OR = 0.17 (0.04-0.73)] without a history of hypertension [OR = 0.34 (0.13-0.91)], and patients who did not take antihypertensive therapy [OR = 0.35 (0.14-0.86)]. CONCLUSION: Our data suggest that orthostatic hypertension may be a protective factor for TIA among younger and normotensive patients.

Association between different methods of assessing blood pressure variability and incident cardiovascular disease, cardiovascular mortality and all-cause mortality: a systematic review.

BACKGROUND: Blood pressure variability (BPV) is a possible risk factor for adverse cardiovascular outcomes and mortality. There is uncertainty as to whether BPV is related to differences in populations studied, measurement methods or both. We systematically reviewed the evidence for different methods to assess blood pressure variability (BPV) and their association with future cardiovascular events, cardiovascular mortality and all-cause mortality. METHODS: Literature databases were searched to June 2019. Observational studies were eligible if they measured short-term BPV, defined as variability in blood pressure measurements acquired either over a 24-hour period or several days. Data were extracted on method of BPV and reported association (or not) on future cardiovascular events, cardiovascular mortality and all-cause mortality. Methodological quality was assessed using the CASP observational study tool and data narratively synthesised. RESULTS: Sixty-one studies including 3,333,801 individuals were eligible. BPV has been assessed by various methods including ambulatory and home-based BP monitors assessing 24-hour, "day-by-day" and "week-to-week" variability. There was moderate quality evidence of an association between BPV and cardiovascular events (43 studies analysed) or all-cause mortality (26 studies analysed) irrespective of the measurement method in the short- to longer-term. There was moderate quality evidence reporting inconsistent findings on the potential association between cardiovascular mortality, irrespective of methods of BPV assessment (17 studies analysed). CONCLUSION: An association between BPV, cardiovascular mortality and cardiovascular events and/or all-cause mortality were reported by the majority of studies irrespective of method of measurement. Direct comparisons between studies and reporting of pooled effect sizes were not possible.

Can cardiovascular risk management be improved by shared care with general practice to prevent cognitive decline following stroke/TIA? A feasibility randomised controlled trial (SERVED memory).

BACKGROUND: Cognitive impairment and dementia following cerebrovascular disease are increasingly common in the UK. One potential strategy to prevent post-stroke cognitive decline is multimodal vascular risk factor management. However, its efficacy remains uncertain and its application in vulnerable patients with incident cerebrovascular disease and early cognitive impairment has not been assessed. The primary aim of this study was to assess the feasibility of recruitment and retention of patients with early cognitive impairment post-stroke or transient ischaemic attack (TIA) to a trial of enhanced vascular risk factor management combining primary and secondary care. METHODS: In this single centre, open label trial adults with a recent stroke or TIA and mild cognitive impairment (MCI) were randomised 1:1 to a three-monthly multimodal vascular risk factor intervention jointly delivered by the trial team and General Practitioner (GP), or control (defined as usual care from the GP). Chosen risk factors were blood pressure (BP), total cholesterol, blood glucose (HbA1C) in those with diabetes, and heart rate and adequacy of anticoagulation in those with atrial fibrillation (AF). Similar patients with normal cognition were enrolled in an embedded observational cohort and also received usual care from the GP. Repeat cognitive screening was undertaken in all participants after 12 months. RESULTS: Seventy three participants were recruited to the randomised trial and 94 to the observational cohort (21.8% of those screened). From the randomised trial 35/73 (47.9%) dropped out before final follow-up. In all groups guideline based rates of risk factor control were mostly poor at baseline and did not significantly improve during follow-up. The observational cohort demonstrated greater decline in cognitive test scores at 12 months, with no difference between the randomised groups. CONCLUSIONS: Recruitment to such a study was feasible, but retention of participants was difficult and generally poor rates of risk factor control suggested insufficient application of the intervention. Consequently, successful scaling up of the trial would require protocol changes with less reliance on primary care services. Any future trial should include participants with normal cognition post-stroke as they may be at greatest risk of cognitive decline. TRIAL REGISTRATION: ISRCTN, ISRCTN42688361 . Registered 16 April 2015.

Individual and Combined Impact of Heart Failure and Atrial Fibrillation on Ischemic Stroke Outcomes.

Background and Purpose- We aimed to determine individual and combined effects of atrial fibrillation (AF) and heart failure (HF) on acute ischemic stroke outcomes: in-hospital mortality, length-of-stay, and poststroke disability; long-term mortality and stroke recurrence. Methods- Prospective cohort study of patients with acute ischemic stroke admitted to a UK center with a catchment population of ≈900 000 between 2004 and 2016. Exposure groups were patients with neither AF nor HF (reference group), those with AF but without HF, those with HF but without AF, and those with AF+HF. Logistic and Cox regressions were used to model in-hospital and long-term outcomes, respectively. Results- A total of 10 816 patients with a mean age±SD =77.9±12.1 years, 48% male were included. Only 30 (4.9%) of the patients with HF but not AF were anticoagulated at discharge. Both AF (odds ratio, 1.24 [95% CI, 1.07-1.43]), HF (odds ratio, 1.40 [1.10-1.79]), and their combination (odds ratio, 2.23 [1.83-2.72]) were associated with increased odds of in-hospital mortality. All 3 exposure groups were associated with increased length-of-stay, while only AF predicted increased disability (1.36 [1.12-1.64]). Patients were followed for a median of 5.5 and 3.7 years for mortality and recurrence, respectively. Long-term mortality was associated with AF (hazard ratio, 1.45 [95% CI, 1.33-1.59]), HF (2.07 [1.83-2.36]), and their combination (2.20 [1.96-2.46]). Recurrent stroke was associated with AF 1.50 (1.26-1.78), HF (1.33 [1.01-1.75]), and AF with HF (1.62 [1.28-2.07]). Conclusions- The AF-associated excess risk of stroke recurrence was independent of comorbid HF. HF without AF was also associated with a significant risk of recurrence. Anticoagulation for secondary stroke prevention in patients with HF without AF may require further evaluation in a clinical trial setting.

Blood pressure differences between home monitoring and daytime ambulatory values and their reproducibility in treated hypertensive stroke and TIA patients.

BACKGROUND: Guidelines recommend ambulatory or home blood pressure monitoring to improve hypertension diagnosis and monitoring. Both these methods are ascribed the same threshold values, but whether they produce similar results has not been established in certain patient groups. METHODS: Adults with mild/moderate stroke or transient ischemic attack (N = 80) completed 2 sets of ambulatory and home blood pressure monitoring. Systolic and diastolic blood pressure values from contemporaneous measurements were compared, and the limits of agreement were assessed. Exploratory analyses for predictive factors of any difference were conducted. RESULTS: Daytime ambulatory blood pressure values were consistently lower than home values, the mean difference in systolic blood pressure for initial ambulatory versus first home monitoring was -6.6 ± 13.5 mm Hg (P≤.001), and final ambulatory versus second home monitoring was -7.1 ± 11.0mm Hg (P≤.001). Mean diastolic blood pressure differences were -2.1 ± 8.5mm Hg (P=.03) and -2.0 ± 7.2mm Hg (P=.02). Limits of agreement for systolic blood pressure were -33.0 to 19.9mm Hg and -28.7 to 14.5mm Hg for the 2 comparisons and for DBP were -18.8 to 14.5mm Hg and -16.1 to 12.2mm Hg, respectively. The individual mean change in systolic blood pressure difference was 11.0 ± 8.3mm Hg across the 2 comparisons. No predictive factors for these differences were identified. CONCLUSIONS: Daytime ambulatory systolic and diastolic blood pressure values were significantly lower than home monitored values at both time points. Differences between the 2 methods were not reproducible for individuals. Using the same threshold value for both out-of-office measurement methods may not be appropriate in patients with cerebrovascular disease.

Myocardial infarction after acute ischaemic stroke: Incidence, mortality and risk factors.

OBJECTIVES: To determine the risk factor profiles associated with post-acute ischaemic stroke (AIS) myocardial infarction (MI) over long-term follow-up. METHODS: This observational study includes prospectively identified AIS patients (n = 9840) admitted to a UK regional centre between January 2003 and December 2016 (median follow-up: 4.72 years). Predictors of post-stroke MI during follow-up were examined using logistic and Cox regression models for in-hospital and post-discharge events, respectively. MI incidence was determined using a competing risk non-parametric estimator. The influence of post-stroke MI on mortality was examined using Cox regressions. RESULTS: Mean age (SD) of study participants was 77.3 (12.2) years (48% males). Factors associated with in-hospital MI (OR [95% CI]) were increasing blood glucose (1.80 [1.17-2.77] per 10 mmol/L), total leucocyte count (1.25 [1.01-1.54] per 10 × 109 /L) and CRP (1.05 [1.02-1.08] per 10 mg/L increase). Age (HR [95% CI] = 1.03 [1.01-1.06]), coronary heart disease (1.59 [1.01-2.50]), chronic kidney disease (2.58 [1.44-4.63]) and cancers (1.76 [1.08-2.89]) were associated with incident MI between discharge and one-year follow-up. Age (1.02 [1.00-1.03]), diabetes (1.96 [1.38-2.65]), congestive heart failure (2.07 [1.44-2.99]), coronary heart disease (1.81 [1.31-2.50]), hypertension [1.86 (1.24-2.79)] and peripheral vascular disease (2.25 [1.40-3.63]) were associated with incident MI between 1 and 5 years after discharge. Diabetes (2.01 [1.09-3.72]), hypertension (3.69 [1.44-9.45]) and peripheral vascular disease (2.46 [1.02-5.98]) were associated with incident MI between 5 and 10 years after discharge. Cumulative MI incidence over 10 years was 5.4%. MI during all follow-up periods (discharge-1, 1-5, 5-10 years) was associated with increased risk of death (respective HR [95% CI] = 3.26 [2.51-4.15], 1.96 [1.58-2.42] and 1.92 [1.26-2.93]). CONCLUSIONS: In conclusion, prognosis is poor in post-stroke MI. We highlight a range of potential areas to focus preventative efforts.

Does self-monitoring and self-management of blood pressure after stroke or transient ischemic attack improve control? TEST-BP, a randomized controlled trial.

The therapeutic benefit of self-monitoring blood pressure in stroke patients is uncertain. We investigated the effect of self-monitoring with or without guided antihypertensive management compared with usual care in patients with a recent cerebrovascular event. No between-group differences in blood pressure at outcome were found, but blood pressure self-monitoring and management was well tolerated.

Increased diastolic blood pressure is associated with MRI biomarkers of dementia-related brain pathology in normative ageing.

Background: hypertension is a risk for brain ageing, but the mechanisms underlying this effect remain unclear. Magnetic resonance imaging (MRI) detected biomarkers of brain ageing include white matter hyperintensities (WMHs), a marker of cerebrovascular disease, and hippocampal volume, a marker of Alzheimer's disease pathology. Objective: to examine relationships between blood pressure (BP) components and brain pathology in older adults. Subjects: two hundred and twenty-seven members of the Aberdeen 1936 Birth Cohort between ages 64 and 68 years. Methods: BP was assessed biennially between 64 and 68 years and brain MRI performed at 68 years. The risk factors of interest were diastolic and systolic BP and their visit-to-visit variability. Outcomes were WMH abundance and hippocampal volume. Regression models, controlling for confounding factors, examined their relationships. Results: higher diastolic BP predicted increased WMH (ß = 0.13, P = 0.044) and smaller hippocampi (ß = -0.25, P = 0.006). In contrast, increased systolic BP predicted larger hippocampi (ß = 0.22, P = 0.013). Variability of diastolic BP predicted lower hippocampal volume (ß = -0.15, P = 0.033). These relationships were independent of confounding life-course risk factors. Anti-hypertensive medication did not modify these relationships, but was independently associated with increased WMH (ß = 0.17, P = 0.011). Conclusion: increased diastolic BP is associated with biomarkers of both cerebrovascular and Alzheimer's diseases, whereas the role of systolic BP is less clear, with evidence for a protective effect on hippocampal volume. These differing relationships emphasise the importance of considering individual BP components with regard to brain ageing and pathology. Interventions targeting diastolic hypertension and its chronic variability may provide new strategies able to slow the accumulation of these harmful pathologies.

Important factors in predicting mortality outcome from stroke: findings from the Anglia Stroke Clinical Network Evaluation Study.

Background: Although variation in stroke service provision and outcomes have been previously investigated, it is less well known what service characteristics are associated with reduced short- and medium-term mortality. Methods: Data from a prospective multicentre study (2009­12) in eight acute regional NHS trusts with a catchment population of about 2.6 million were used to examine the prognostic value of patient-related factors and service characteristics on stroke mortality outcome at 7, 30 and 365 days post stroke, and time to death within 1 year. Results: A total of 2,388 acute stroke patients (mean (standard deviation) 76.9 (12.7) years; 47.3% men, 87% ischaemic stroke) were included in the study. Among patients characteristics examined increasing age, haemorrhagic stroke, total anterior circulation stroke type, higher prestroke frailty, history of hypertension and ischaemic heart disease and admission hyperglycaemia predicted 1-year mortality. Additional inclusion of stroke service characteristics controlling for patient and service level characteristics showed varying prognostic impact of service characteristics on stroke mortality over the disease course during first year after stroke at different time points. The most consistent finding was the benefit of higher nursing levels; an increase in one trained nurses per 10 beds was associated with reductions in 30-day mortality of 11­28% (P < 0.0001) and in 1-year mortality of 8­12% (P < 0.001). Conclusions: There appears to be consistent and robust evidence of direct clinical benefit on mortality up to 1 year after acute stroke of higher numbers of trained nursing staff over and above that of other recognised mortality risk factors.

Derivation and Validation of a Novel Prognostic Scale (Modified-Stroke Subtype, Oxfordshire Community Stroke Project Classification, Age, and Prestroke Modified Rankin) to Predict Early Mortality in Acute Stroke.

BACKGROUND AND PURPOSE: The stroke subtype, Oxfordshire Community Stroke Project classification, age, and prestroke modified Rankin (SOAR) score is a prognostic scale proposed for early mortality prediction after acute stroke. We aimed to evaluate whether including a measure of initial stroke severity (National Institutes of Health Stroke Scale and modified-SOAR [mSOAR] scores) would improve the prognostic accuracy. METHODS: Using Anglia Stroke and Heart Clinical Network data, 2008 to 2011, we assessed the performance of SOAR and mSOAR against in-hospital mortality using area under the receiver operating curve statistics. We externally validated the prognostic utility of SOAR and mSOAR using an independent cohort data set from Glasgow. We described calibration using Hosmer-Lemeshow goodness-of-fit test. RESULTS: A total of 1002 patients were included in the derivation cohort, and 105 (10.5%) died as inpatients. The area under the receiver operating curves for outcome of early mortality derived from the SOAR and mSOAR scores were 0.79 (95% confidence interval, 0.75-0.84) and 0.83 (95% confidence interval, 0.79-0.86), respectively (P=0.001). The external validation data set contained 1012 patients with stroke; of which, 121 (12.0%) patients died within 90 days. The mSOAR scores identified the risk of early mortality ranging from 3% to 42%. External validation of mSOAR score yielded an area under the receiver operating curve of 0.84 (95% confidence interval, 0.82-0.88) for outcome of early mortality. Calibration was good (P=0.70 for the Hosmer-Lemeshow test). CONCLUSIONS: Adding National Institutes of Health Stroke Scale data to create a modified-SOAR score improved prognostic utility in both derivation and validation data sets. The mSOAR may have clinical utility by using easily available data to predict mortality.

Assessment of platelet function in patients with stroke using multiple electrode platelet aggregometry: a prospective observational study.

BACKGROUND: There is a link between high on-treatment platelet reactivity (HPR) and adverse vascular events in stroke. This study aimed to compare multiple electrode platelet aggregometry (MEA), in healthy subjects and ischaemic stroke patients, and between patients naive to antiplatelet drugs (AP) and those on regular low dose AP. We also aimed to determine prevalence of HPR at baseline and at 3-5 days after loading doses of aspirin. METHODS: Patients with first ever ischaemic stroke were age and sex-matched to a healthy control group. Three venous blood samples were collected: on admission before any treatment given (baseline); at 24 h and 3-5 days after standard treatment. MEA was determined using a Mutliplate® analyser and agonists tested were arachidonic acid (ASPI), adenosine diphosphate (ADP) and collagen (COL). RESULTS: Seventy patients (mean age 73 years [SD 13]; 42 men, 28 women) were age and sex-matched to 72 healthy subjects. Thirty-three patients were on antiplatelet drugs (AP) prior to stroke onset and 37 were AP-naive. MEA results for all agonists were significantly increased in AP-naive patients compared to healthy subjects: ADP 98 ± 31 vs 81 ± 24, p < 0.005; ASPI 117 ± 31 vs 98 ± 27, p < 0.005; COL 100 ± 25 vs 82 ± 20, p < 0.005. For patients on long term AP, 33% (10/30) of patients were considered aspirin-resistant. At 3-5 days following loading doses of aspirin, only 11.1% were aspirin resistant based on an ASPI cut-off value of 40 AU*min. CONCLUSIONS: Many patients receiving low dose aspirin met the criteria of aspirin resistance but this was much lower at 3-5 days following loading doses of aspirin. Future studies are needed to establish the causes of HPR and potential benefits of individualizing AP treatment based on platelet function testing.

Effectiveness of interventions to indirectly support food and drink intake in people with dementia: Eating and Drinking Well IN dementiA (EDWINA) systematic review.

BACKGROUND: Risks and prevalence of malnutrition and dehydration are high in older people but even higher in older people with dementia. In the EDWINA (Eating and Drinking Well IN dementiA) systematic review we aimed to assess effectiveness of interventions aiming to improve, maintain or facilitate food/drink intake indirectly, through food service or dining environment modification, education, exercise or behavioural interventions in people with cognitive impairment or dementia (across all settings, levels of care and support, types and degrees of dementia). METHODS: We comprehensively searched Medline and twelve further databases, plus bibliographies, for intervention studies with ≥3 cognitively impaired adult participants (any type/stage). The review was conducted with service user input in accordance with Cochrane Collaboration's guidelines. We duplicated assessment of inclusion, data extraction, and validity assessment, tabulating data. Meta-analysis (statistical pooling) was not appropriate so data were tabulated and synthesised narratively. RESULTS: We included 56 interventions (reported in 51 studies). Studies were small and there were no clearly effective, or clearly ineffective, interventions. Promising interventions included: eating meals with care-givers, family style meals, soothing mealtime music, constantly accessible snacks and longer mealtimes, education and support for formal and informal care-givers, spaced retrieval and Montessori activities, facilitated breakfast clubs, multisensory exercise and multicomponent interventions. CONCLUSIONS: We found no definitive evidence on effectiveness, or lack of effectiveness, of specific interventions but studies were small and short term. A variety of promising indirect interventions need to be tested in large, high-quality RCTs, and may be approaches that people with dementia and their formal or informal care-givers would wish to try. TRIAL REGISTRATION: The systematic review protocol was registered (CRD42014007611) and is published, with the full MEDLINE search strategy, on Prospero (http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42014007611).

Time to Computerized Tomography Scan, Age, and Mortality in Acute Stroke.

BACKGROUND: Time to computerized tomography (CT) is important to institute appropriate and timely hyperacute management in stroke. We aimed to evaluate mortality outcomes in relation to age and time to CT scan. METHODS: We used routinely collected data in 8 National Health Service trusts in East of England between September 2008 and April 2011. Stroke cases were prospectively identified and confirmed. Odds ratios (ORs) for unadjusted and adjusted models for age categories (<65, 65-74, 75-84, and ≥85 years) as well as time to CT categories (<90 minutes, ≥90 to <180 minutes, ≥180 minutes to 24 hours, and >24 hours) and in-hospital and early (<7 days) mortality outcomes were calculated. RESULTS: Of the 7693 patients (mean age 76.1 years, 50% male) included, 1151 (16%) died as inpatients and 336 (4%) died within 7 days. Older patients and those admitted from care home had a significantly longer time from admission until CT (P < .001). Patients who had earlier CT scans were admitted to stroke units more frequently (P < .001) but had higher in-patient (P < .001) and 7-day mortality (P < .001). Whereas older age was associated with increased odds of mortality outcomes, longer time to CT was associated with significantly reduced mortality within 7 days (corresponding ORs for the above time periods were 1.00, .61 [95% confidence interval {CI}: .39-.95], .39 [.24-.64], and .16 [.08-.33]) and in-hospital mortality (ORs 1.00, .86 [.64-1.15], .57 [.42-.78] and .71 [.52-.98]). CONCLUSIONS: Older age was associated with a significantly longer time to CT. However, using CT scan time as a benchmarking tool in stroke may have inherent limitations and does not appear to be a suitable quality marker.

Prognostic Significance of Short-Term Blood Pressure Variability in Acute Stroke: Systematic Review.

BACKGROUND AND PURPOSE: Blood pressure variability (BPV) may be an important prognostic factor acutely after stroke. This review investigated the existing evidence for the effect of BPV on outcome after stroke, also considering BPV measurement techniques and definitions. METHODS: A literature search was performed according to a prespecified study protocol. Two reviewers independently assessed study eligibility and quality. Where appropriate, meta-analyses were performed to assess the effect of BPV on poor functional outcome. RESULTS: Eighteen studies from 1359 identified citations were included. Seven studies were included in a meta-analysis for the effect of BPV on functional outcome (death or disability). Systolic BPV was significantly associated with poor functional outcome: pooled odds ratio per 10-mm Hg increment, 1.2; confidence interval (1.1-1.3). A descriptive review of included studies also supports these findings, and in addition, it suggests that systolic BPV may be associated with increased risk of intracranial hemorrhage in those treated with thrombolytic therapy. CONCLUSIONS: This systematic review and meta-analysis suggest that greater systolic BPV, measured early from ischemic stroke or intracerebral hemorrhage onset, is associated with poor longer-term functional outcome. Future prospective studies should investigate how best to measure and define BPV in acute stroke, as well as to determine its prognostic significance.

The clinical utility of Multiplate analyser measurement in platelet function testing following stroke and transient ischaemic attack.

BACKGROUND: Platelet responsiveness to aspirin in people with cerebrovascular disease is poorly understood. OBJECTIVES: To determine: (i) normal reference range, imprecision and reproducibility of the Multiplate instrument in healthy volunteers naive to aspirin; (ii) imprecision and reproducibility of the Multiplate instrument in acute stroke and transient ischaemic attack (TIA); (iii) the relationship between aspirin responsiveness and clinical outcome. MATERIALS AND METHODS: We evaluated platelet function response to three agonists [Adenosine Diphosphate (ADP), Arachidonic Acid (AA), Collagen (Col)] using the Mulitplate platelet function analyser in a two-phase pilot study. In phase 1, we recruited healthy volunteers to determine the normal reference range and imprecision of the Multiplate instrument. In phase 2, we assessed platelet function in acute stroke or TIA patients presenting to hospital. These patients were bled within 24 h of presentation and between 12 and 24 h after ≥75 mg dose of Aspirin. Patients were followed up to 1 yr to assess mortality and recurrent cardiovascular event. RESULTS: Overall, 29 healthy volunteers and 81 stroke/TIA patients were recruited. On assessing components of variance, Multiplate testing is reproducible and precise in volunteers and stroke/TIA patients. In stroke patients receiving aspirin, Bland-Altman plots show initial day 1 measurement provided a reliable measure of continuing response to aspirin at day 3. We defined one-third of patients as aspirin resistant [31.8% (95% CI: 22.1%-42.8%)] using cut off mean aggregation of ≥23.08% for AA and mean aggregation of ≥80.76% for ADP. CONCLUSION: The Multiplate device gives reproducible, precise results in volunteers and stroke/TIA patients.

The changes in clot microstructure in patients with ischaemic stroke and the effects of therapeutic intervention: a prospective observational study.

BACKGROUND: Stroke is the second largest cause of death worldwide. Hypercoagulability is a key feature in ischaemic stroke due to the development of an abnormally dense clot structure but techniques assessing the mechanics and quality of clot microstructure have limited clinical use. We have previously validated a new haemorheological technique using three parameters to reflect clot microstructure (Fractal Dimension (d f )) ex-vivo, real-time clot formation time (T GP ) and blood clot strength (elasticity at the gel point (G'GP)). We aimed to evaluate these novel clotting biomarkers in ischaemic stroke and changes of clot structure following therapeutic intervention. METHODS: In a prospective cohort study clot microstructure was compared in ischaemic stroke patients and a control group of healthy volunteers. Further assessment took place at 2-4 hours and at 24 hours after therapeutic intervention in the stroke group to assess the effects of thrombolysis and anti-platelet therapy. RESULTS: 75 patients (mean age 72.8 years [SD 13.1]; 47 male, 28 female) with ischaemic stroke were recruited. Of the 75 patients, 32 were thrombolysed with t-PA and 43 were loaded with 300 mg aspirin. The following parameters were significantly different between patients with stroke and the 74 healthy subjects: d f (1.760 ± .053 versus 1.735 ± 0.048, p = 0.003), TGP (208 ± 67 versus 231 ± 75, p = 0.05), G'GP (0.056 ± 0.017 versus 0.045 ± 0.014, p < 0.0001) and fibrinogen (3.7 ± 0.8 versus 3.2 ± 0.5, p < 0.00001). There was a significant decrease in d f (p = 0.02), G'GP (p = 0.01) and fibrinogen (p = 0.01) following the administration of aspirin and for d f (p = 0.003) and fibrinogen (p < 0.001) following thrombolysis as compared to baseline values. CONCLUSION: Patients with ischaemic stroke have denser and stronger clot structure as detected by d f and G'GP. The effect of thrombolysis on clot microstructure (d f ) was more prominent than antiplatelet therapy. Further work is needed to assess the clinical and therapeutic implications of these novel biomarkers.

Clinical symptoms, signs and tests for identification of impending and current water-loss dehydration in older people.

BACKGROUND: There is evidence that water-loss dehydration is common in older people and associated with many causes of morbidity and mortality. However, it is unclear what clinical symptoms, signs and tests may be used to identify early dehydration in older people, so that support can be mobilised to improve hydration before health and well-being are compromised. OBJECTIVES: To determine the diagnostic accuracy of state (one time), minimally invasive clinical symptoms, signs and tests to be used as screening tests for detecting water-loss dehydration in older people by systematically reviewing studies that have measured a reference standard and at least one index test in people aged 65 years and over. Water-loss dehydration was defined primarily as including everyone with either impending or current water-loss dehydration (including all those with serum osmolality ≥ 295 mOsm/kg as being dehydrated). SEARCH METHODS: Structured search strategies were developed for MEDLINE (OvidSP), EMBASE (OvidSP), CINAHL, LILACS, DARE and HTA databases (The Cochrane Library), and the International Clinical Trials Registry Platform (ICTRP). Reference lists of included studies and identified relevant reviews were checked. Authors of included studies were contacted for details of further studies. SELECTION CRITERIA: Titles and abstracts were scanned and all potentially relevant studies obtained in full text. Inclusion of full text studies was assessed independently in duplicate, and disagreements resolved by a third author. We wrote to authors of all studies that appeared to have collected data on at least one reference standard and at least one index test, and in at least 10 people aged ≥ 65 years, even where no comparative analysis has been published, requesting original dataset so we could create 2 x 2 tables. DATA COLLECTION AND ANALYSIS: Diagnostic accuracy of each test was assessed against the best available reference standard for water-loss dehydration (serum or plasma osmolality cut-off ≥ 295 mOsm/kg, serum osmolarity or weight change) within each study. For each index test study data were presented in forest plots of sensitivity and specificity. The primary target condition was water-loss dehydration (including either impending or current water-loss dehydration). Secondary target conditions were intended as current (> 300 mOsm/kg) and impending (295 to 300 mOsm/kg) water-loss dehydration, but restricted to current dehydration in the final review.We conducted bivariate random-effects meta-analyses (Stata/IC, StataCorp) for index tests where there were at least four studies and study datasets could be pooled to construct sensitivity and specificity summary estimates. We assigned the same approach for index tests with continuous outcome data for each of three pre-specified cut-off points investigated.Pre-set minimum sensitivity of a useful test was 60%, minimum specificity 75%. As pre-specifying three cut-offs for each continuous test may have led to missing a cut-off with useful sensitivity and specificity, we conducted post-hoc exploratory analyses to create receiver operating characteristic (ROC) curves where there appeared some possibility of a useful cut-off missed by the original three. These analyses enabled assessment of which tests may be worth assessing in further research. A further exploratory analysis assessed the value of combining the best two index tests where each had some individual predictive ability. MAIN RESULTS: There were few published studies of the diagnostic accuracy of state (one time), minimally invasive clinical symptoms, signs or tests to be used as screening tests for detecting water-loss dehydration in older people. Therefore, to complete this review we sought, analysed and included raw datasets that included a reference standard and an index test in people aged ≥ 65 years.We included three studies with published diagnostic accuracy data and a further 21 studies provided datasets that we analysed. We assessed 67 tests (at three cut-offs for each continuous outcome) for diagnostic accuracy of water-loss dehydration (primary target condition) and of current dehydration (secondary target condition).Only three tests showed any ability to diagnose water-loss dehydration (including both impending and current water-loss dehydration) as stand-alone tests: expressing fatigue (sensitivity 0.71 (95% CI 0.29 to 0.96), specificity 0.75 (95% CI 0.63 to 0.85), in one study with 71 participants, but two additional studies had lower sensitivity); missing drinks between meals (sensitivity 1.00 (95% CI 0.59 to 1.00), specificity 0.77 (95% CI 0.64 to 0.86), in one study with 71 participants) and BIA resistance at 50 kHz (sensitivities 1.00 (95% CI 0.48 to 1.00) and 0.71 (95% CI 0.44 to 0.90) and specificities of 1.00 (95% CI 0.69 to 1.00) and 0.80 (95% CI 0.28 to 0.99) in 15 and 22 people respectively for two studies, but with sensitivities of 0.54 (95% CI 0.25 to 0.81) and 0.69 (95% CI 0.56 to 0.79) and specificities of 0.50 (95% CI 0.16 to 0.84) and 0.19 (95% CI 0.17 to 0.21) in 21 and 1947 people respectively in two other studies). In post-hoc ROC plots drinks intake, urine osmolality and axillial moisture also showed limited diagnostic accuracy. No test was consistently useful in more than one study.Combining two tests so that an individual both missed some drinks between meals and expressed fatigue was sensitive at 0.71 (95% CI 0.29 to 0.96) and specific at 0.92 (95% CI 0.83 to 0.97).There was sufficient evidence to suggest that several stand-alone tests often used to assess dehydration in older people (including fluid intake, urine specific gravity, urine colour, urine volume, heart rate, dry mouth, feeling thirsty and BIA assessment of intracellular water or extracellular water) are not useful, and should not be relied on individually as ways of assessing presence or absence of dehydration in older people.No tests were found consistently useful in diagnosing current water-loss dehydration. AUTHORS' CONCLUSIONS: There is limited evidence of the diagnostic utility of any individual clinical symptom, sign or test or combination of tests to indicate water-loss dehydration in older people. Individual tests should not be used in this population to indicate dehydration; they miss a high proportion of people with dehydration, and wrongly label those who are adequately hydrated.Promising tests identified by this review need to be further assessed, as do new methods in development. Combining several tests may improve diagnostic accuracy.

Prospective evaluation of blood coagulability and effect of treatment in patients with stroke using rotational thromboelastometry.

BACKGROUND: Stroke is the second largest cause of death worldwide. Abnormalities in hemostasis play an important role in the pathophysiology of ischemic stroke (IS). These hemostatic defects can be detected using rotational thromboelastometry (ROTEM) as a global method of measuring coagulation. This study assessed the effects of IS on blood hypercoagulability using ROTEM method, before and subsequent to therapeutic interventions. METHODS: In a prospective observational cohort study, whole blood coagulation using ROTEM, along with full blood count and standard coagulation tests, were compared between patients with IS and an age-matched control group of healthy volunteers. Further assessment took place at 2-4 hours and at 24 hours in the stroke group after therapy to assess the effects of therapeutic intervention. RESULTS: Seventy-two patients with IS were age-matched to 71 healthy subjects. Clotting time (CT) INTEM (P = .01) and maximum clot firmness (MCF) INTEM (P = .02) were significantly different between stroke patients at baseline and healthy subjects, but this difference disappeared when controlled for by smoking status. There was no association between ROTEM parameters and time from stroke symptom onset or stroke severity as reflected in The National Institute of Health Stroke Scale score. Significant but small changes in the values of MCF-EXTEM, clot formation time (CFT) EXTEM, and alpha-EXTEM CT were observed after therapeutic intervention (thrombolysis or aspirin treatment). CONCLUSIONS: ROTEM testing does not seem to detect a hypercoagulable state in patients with IS. Nonetheless, some ROTEM parameters had a small change after antiplatelet therapy or thrombolysis.

A simple 5-point scoring system, NaURSE (Na+, urea, respiratory rate and shock index in the elderly), predicts in-hospital mortality in oldest old.

BACKGROUND: the mortality is high in acutely ill oldest old patients. Understanding the prognostic factors which influence mortality will help clinicians make appropriate management decisions. METHODS: we analysed prospective mortality audit data (November 2008 to January 2009) to identify variables associated with in-patient mortality in oldest old. We selected those with P < 0.10 from univariate analysis and determined at which cut-point they served as the strongest predictor of mortality. Using these cut-off points, we constructed multivariate logistic regression models. A 5-point score was derived from cut-off points which were significantly associated with mortality tested in a smaller independent re-audit sample conducted in October 2011. RESULTS: a total of 405 patients (mean 93.5 ± 2.7 years) were included in the study. The mean length of stay was 18.5 ± 42.4 days and 13.8% died as in-patients. Variables (cut-off values) found to be significantly associated with in-patient mortality were admission sodium (>145 mmol/l), urea (≥14 mmol/l), respiratory rate (>20/min) and shock index (>1.0): creating a 5-point score (NaURSE: NaURS in the Elderly). The crude mortality rates were 9.5, 19.9, 34.4, 66.7, and 100% for scores 0, 1, 2, 3 and 4, respectively. Using the cut-off point of ≥2, the NaURSE score has a specificity of 87% (83.1-90.3) and sensitivity of 39% (28.5-50.0), with an AUC value of 0.69 (0.63-0.76). An external independent validation study (n = 121) showed similar results. CONCLUSIONS: the NaURSE score may be particularly useful in identifying oldest old who are likely to die in that admission to guide appropriate care.