Bridging the age gap in breast cancer: cluster randomized trial of two decision support interventions for older women with operable breast cancer on quality of life, survival, decision quality, and treatment choices.

BACKGROUND: Rates of surgery and adjuvant therapy for breast cancer vary widely between breast units. This may contribute to differences in survival. This cluster RCT evaluated the impact of decision support interventions (DESIs) for older women with breast cancer, to ascertain whether DESIs influenced quality of life, survival, decision quality, and treatment choice. METHODS: A multicentre cluster RCT compared the use of two DESIs against usual care in treatment decision-making in older women (aged at least ≥70 years) with breast cancer. Each DESI comprised an online algorithm, booklet, and brief decision aid to inform choices between surgery plus adjuvant endocrine therapy versus primary endocrine therapy, and adjuvant chemotherapy versus no chemotherapy. The primary outcome was quality of life. Secondary outcomes included decision quality measures, survival, and treatment choice. RESULTS: A total of 46 breast units were randomized (21 intervention, 25 usual care), recruiting 1339 women (670 intervention, 669 usual care). There was no significant difference in global quality of life at 6 months after the baseline assessment on intention-to-treat analysis (difference -0.20, 95 per cent confidence interval (C.I.) -2.69 to 2.29; P = 0.900). In women offered a choice of primary endocrine therapy versus surgery plus endocrine therapy, knowledge about treatments was greater in the intervention arm (94 versus 74 per cent; P = 0.003). Treatment choice was altered, with a primary endocrine therapy rate among women with oestrogen receptor-positive disease of 21.0 per cent in the intervention versus 15.4 per cent in usual-care sites (difference 5.5 (95 per cent C.I. 1.1 to 10.0) per cent; P = 0.029). The chemotherapy rate was 10.3 per cent at intervention versus 14.8 per cent at usual-care sites (difference -4.5 (C.I. -8.0 to 0) per cent; P = 0.013). Survival was similar in both arms. CONCLUSION: The use of DESIs in older women increases knowledge of breast cancer treatment options, facilitates shared decision-making, and alters treatment selection. Trial registration numbers: EudraCT 2015-004220-61 (https://eudract.ema.europa.eu/), ISRCTN46099296 (http://www.controlled-trials.com).

Dynamic cerebral autoregulation is impaired during submaximal isometric handgrip in patients with heart failure.

The incidence of neurological complications, including stroke and cognitive dysfunction, is elevated in patients with heart failure (HF) with reduced ejection fraction. We hypothesized that the cerebrovascular response to isometric handgrip (iHG) is altered in patients with HF. Adults with HF and healthy volunteers were included. Cerebral blood velocity (CBV; transcranial Doppler, middle cerebral artery) and arterial blood pressure (BP; Finometer) were continuously recorded supine for 6 min, corresponding to 1 min of baseline and 3 min of iHG exercise, at 30% maximum voluntary contraction, followed by 2 min of recovery. The resistance-area product was calculated from the instantaneous BP-CBV relationship. Dynamic cerebral autoregulation (dCA) was assessed with the time-varying autoregulation index estimated from the CBV step response derived by an autoregressive moving-average time-domain model. Forty patients with HF and 23 BP-matched healthy volunteers were studied. Median left ventricular ejection fraction was 38.5% (interquartile range: 0.075%) in the HF group. Compared with control subjects, patients with HF exhibited lower time-varying autoregulation index during iHG, indicating impaired dCA ( P < 0.025). During iHG, there were steep rises in CBV, BP, and heart rate in control subjects but with different temporal patterns in HF, which, together with the temporal evolution of resistance-area product, confirmed the disturbance in dCA in HF. Patients with HF were more likely to have impaired dCA during iHG compared with age-matched control subjects. Our results also suggest an impairment of myogenic, neurogenic, and metabolic control mechanisms in HF. The relationship between impaired dCA and neurological complications in patients with HF during exercise deserves further investigation. NEW & NOTEWORTHY Our findings provide the first direct evidence that cerebral blood flow regulatory mechanisms can be affected in patients with heart failure during isometric handgrip exercise. As a consequence, eventual blood pressure modulations are buffered less efficiently and metabolic demands may not be met during common daily activities. These deficits in cerebral autoregulation are compounded by limitations of the systemic response to isometric exercise, suggesting that patients with heart failure may be at greater risk for cerebral events during exercise.

How many squat-stand manoeuvres to assess dynamic cerebral autoregulation?

PURPOSE: Squat-stand manoeuvres (SSMs) have been used to induce blood pressure (BP) changes for the reliable assessment of dynamic cerebral autoregulation. However, they are physically demanding and thus multiple manoeuvres can be challenging for older subjects. This study aimed to determine the minimum number of SSMs required to obtain satisfactory coherence, thus minimising the subjects' workload. METHOD: 20 subjects performed SSMs at a frequency of 0.05 Hz. End-tidal CO2, cerebral blood flow velocity, heart rate, continuous BP and the depth of the squat were measured. 11 subjects returned for a repeat visit. The time points at which subjects had performed 3, 6, 9, 12 and 15 SSMs were determined. Transfer function analysis was performed on files altered to the required length to obtain estimates of coherence and the autoregulation index (ARI). RESULTS: After three SSMs, coherence (0.05 Hz) was 0.93 ± 0.05, and peaked at 0.95 ± 0.02 after 12 manoeuvres. ARI decreased consecutively with more manoeuvres. ARI was comparable across the two visits (p = 0.92), but coherence was significantly enhanced during the second visit (p < 0.01). The intra-subject coefficients of variation (CoV) for ARI remained comparable as the number of manoeuvres varied. CONCLUSIONS: This analysis can aid those designing SSM protocols, especially where participants are unable to tolerate a standard 5-min protocol or when a shorter protocol is needed to accommodate additional tests. We emphasise that fewer manoeuvres should only be used in exceptional circumstances, and where possible a full set of manoeuvres should be performed. Furthermore, these results need replicating at 0.10 Hz to ensure their applicability to different protocols.

Cerebral blood flow autoregulation in ischemic heart failure.

Patients with ischemic heart failure (iHF) have a high risk of neurological complications such as cognitive impairment and stroke. We hypothesized that iHF patients have a higher incidence of impaired dynamic cerebral autoregulation (dCA). Adult patients with iHF and healthy volunteers were included. Cerebral blood flow velocity (CBFV, transcranial Doppler, middle cerebral artery), end-tidal CO2 (capnography), and arterial blood pressure (Finometer) were continuously recorded supine for 5 min at rest. Autoregulation index (ARI) was estimated from the CBFV step response derived by transfer function analysis using standard template curves. Fifty-two iHF patients and 54 age-, gender-, and BP-matched healthy volunteers were studied. Echocardiogram ejection fraction was 40 (20-45) % in iHF group. iHF patients compared with control subjects had reduced end-tidal CO2 (34.1 ± 3.7 vs. 38.3 ± 4.0 mmHg, P < 0.001) and lower ARI values (5.1 ± 1.6 vs. 5.9 ± 1.0, P = 0.012). ARI <4, suggestive of impaired CA, was more common in iHF patients (28.8 vs. 7.4%, P = 0.004). These results confirm that iHF patients are more likely to have impaired dCA compared with age-matched controls. The relationship between impaired dCA and neurological complications in iHF patients deserves further investigation.

Post-Carotid Endarterectomy Hypertension. Part 1: Association with Pre-operative Clinical, Imaging, and Physiological Parameters.

OBJECTIVE/BACKGROUND: Post-endarterectomy hypertension (PEH) is a well recognised, but poorly understood, phenomenon after carotid endarterectomy (CEA) that is associated with post-operative intracranial haemorrhage, hyperperfusion syndrome, and cardiac complications. The aim of the current study was to identify pre-operative clinical, imaging, and physiological parameters associated with PEH. METHODS: In total, 106 CEA patients undergoing CEA under general anaesthesia underwent pre-operative evaluation of 24 hour ambulatory arterial blood pressure (BP), baroreceptor sensitivity, cerebral autoregulation, and transcranial Doppler measurement of cerebral blood flow velocity (CBFv) and pulsatility index. Patients who met pre-existing criteria for treating PEH after CEA (systolic BP [SBP] > 170 mmHg without symptoms or SBP > 160 mmHg with headache/seizure/neurological deficit) were treated according to a previously established protocol. RESULTS: In total, 40/106 patients (38%) required treatment for PEH at some stage following CEA (26 in theatre recovery [25%], 27 while on the vascular surgical ward [25%]), while seven (7%) had SBP surges > 200 mmHg back on the ward. Patients requiring treatment for PEH had a significantly higher pre-operative SBP (144 ± 11 mmHg vs. 135 ± 13 mmHg; p < .001) and evidence of pre-existing impairment of baroreceptor sensitivity (3.4 ± 1.7 ms/mmHg vs. 5.3 ± 2.8 ms/mmHg; p = .02). However, PEH was not associated with any other pre-operative clinical features, CBFv, or impaired cerebral haemodynamics. Paradoxically, autoregulation was better preserved in patients with PEH. All four cases of hyperperfusion associated symptoms were preceded by PEH. Length of hospital stay was significantly increased in patients with PEH (p < .001). CONCLUSION: In this study, where all patients underwent CEA under general anaesthesia, PEH was associated with poorly controlled pre-operative BP and impaired baroreceptor sensitivity, but not with other peripheral or central haemodynamic parameters, including impaired cerebral autoregulation.

Cerebral Hemodynamic Effects of Cheyne-Stokes Respiration in a Patient with Stroke.

INTRODUCTION: Cheyne-Stokes respiration (CSR) and central sleep apnea (CSA) are common in patients with heart failure and/or stroke. We aim to describe the cerebrovascular effects of CSR during the acute phase of stroke in a heart failure patient. CASE REPORT: A 74-year-old male with previous dilated cardiomyopathy had sudden onset of right hemiparesis and aphasia. A transcranial Doppler was performed with continuous measurement of blood pressure (BP) (Finometer) and end-tidal CO2 (nasal capnography). Offline analysis of hemodynamic data disclosed relatively large periodic oscillations of both cerebral blood flow velocity and BP related to the CSR breathing pattern. Derivate variables from the cerebrovascular resistance were calculated (critical closing pressure and resistance-area product), demonstrating that there may be a myogenic impairment of cerebral blood flow (CBF) control in the affected hemisphere of this subgroup of patient. CONCLUSION: There is an impairment of CBF regulation in the affected hemisphere of the patient with ischemic stroke and CSR, highlighting the role of cerebral hemodynamic monitoring in this scenario.

Gene and Protein Expression of Chemokine (C-C-Motif) Ligand 19 is Upregulated in Unstable Carotid Atherosclerotic Plaques.

OBJECTIVE/BACKGROUND: The aim was to investigate the expression of genes associated with carotid plaque instability and their protein products at a local and systemic level. METHODS: Carotid plaques from 24 patients undergoing carotid endarterectomy (CEA) were classified as stable or unstable using clinical, histological, ultrasound, and transcranial Doppler criteria, and compared using whole genome microarray chips. Initial results of differentially expressed genes were validated by quantitative reverse transcriptase polymerase chain reaction in an independent group of 96 patients undergoing CEA. The protein product of genes significantly differentially expressed between patients with stable and unstable plaques were analysed by plaque immunohistochemistry and serum protein quantification by enzyme-linked immunosorbent assay on a further independent cohort. RESULTS: Expression of chemokine (c-c-motif) ligand 19 (CCL19) was significantly upregulated in plaques from patients with clinically unstable disease (p < .001). Cathepsin G expression was upregulated in histologically unstable plaques (p = .04). Serum concentration of CCL19 was significantly higher in patients with clinically unstable plaques (p = .02). Immunohistochemical staining for CCL19 demonstrated positive staining in histologically and clinically unstable plaques (p = .03). CCL19 also co-localised with CD3+ T-cell lymphocytes in the core region, around where CCL19 was expressed. CONCLUSIONS: CCL19 is significantly overexpressed in patients with unstable carotid atherosclerotic plaques and may be a possible novel biomarker for identifying high-risk patients in whom more urgent intervention may be indicated.

Cerebrovascular effects of the thigh cuff maneuver.

Arterial hypotension can be induced by sudden release of inflated thigh cuffs (THC), but its effects on the cerebral circulation have not been fully described. In nine healthy subjects [aged 59 (9) yr], bilateral cerebral blood flow velocity (CBFV) was recorded in the middle cerebral artery (MCA), noninvasive arterial blood pressure (BP) in the finger, and end-tidal CO2 (ETCO2) with nasal capnography. Three THC maneuvers were performed in each subject with cuff inflation 20 mmHg above systolic BP for 3 min before release. Beat-to-beat values were extracted for mean CBFV, BP, ETCO2 , critical closing pressure (CrCP), resistance-area product (RAP), and heart rate (HR). Time-varying estimates of the autoregulation index [ARI(t)] were also obtained using an autoregressive-moving average model. Coherent averages synchronized by the instant of cuff release showed significant drops in mean BP, CBFV, and RAP with rapid return of CBFV to baseline. HR, ETCO2 , and ARI(t) were transiently increased, but CrCP remained relatively constant. Mean values of ARI(t) for the 30 s following cuff release were not significantly different from the classical ARI [right MCA 5.9 (1.1) vs. 5.1 (1.6); left MCA 5.5 (1.4) vs. 4.9 (1.7)]. HR was strongly correlated with the ARI(t) peak after THC release (in 17/22 and 21/24 recordings), and ETCO2 was correlated with the subsequent drop in ARI(t) (19/22 and 20/24 recordings). These results suggest a complex cerebral autoregulatory response to the THC maneuver, dominated by myogenic mechanisms and influenced by concurrent changes in ETCO2 and possible involvement of the autonomic nervous system and baroreflex.

Comprehensive Geriatric Assessment and predicted 3-year survival in treatment planning for frail patients with early breast cancer.

BACKGROUND: Endocrine therapy alone has been a popular treatment for oestrogen receptor-positive breast cancer in elderly patients, although it may be inadequate in those surviving more than 2-3 years. The aim of this study was to estimate 3-year survival in frail patients with early breast cancer, to inform treatment decisions. METHODS: A risk score was created to estimate 3-year survival in individual patients using data from patients who had Comprehensive Geriatric Assessment (CGA) in a specialist clinic before decisions about their breast cancer treatment were made. The data were analysed using logistic regression. RESULTS: Ninety-seven (29·6 per cent) of the 328 patients had died by 3 years. Four components of the assessment proved strongly associated with survival: Mini Mental State Examination, Barthel Index of Activities of Daily Living, instrumental Activities of Daily Living and American Association of Anesthesiologists fitness grade. The derived CGA risk score gave an adequate level of discrimination and calibration, with an area under the receiver operating characteristic (ROC) curve of 0·75 (95 per cent c.i. 0·67 to 0·82) (Hosmer-Lemeshow statistic χ(2) = 7·9, P = 0·448). CONCLUSION: Detailed assessment can allow prediction of survival probability in frail elderly patients. Good scores indicate good survival prospects and a likely benefit from surgery; poor scores are associated with reduced survival, although with wide variation. CGA is recommended before making decisions on best treatment.

A Novel Ultrasound-Based Carotid Plaque Risk Index Associated with the Presence of Cerebrovascular Symptoms.

PURPOSE: The purpose of this study was to determine the efficacy of a novel ultrasound-based carotid plaque risk index (CPRI) in predicting the presence of cerebrovascular symptoms in patients with carotid artery stenosis. MATERIALS AND METHODS: This was a cross-sectional, observational study involving 56 patients (mean age 76.6 years, 62.5 % male). Plaque grayscale median (GSM) and surface irregularity indices (SII) were measured in 82 stenosed carotid arteries (range 10 - 95 %) and combined with the degree of stenosis (DOS) in the form of (DOS*SII)/(1 + GSM). A reduced index DOS/(1 + GSM) not incorporating plaque surface irregularities was also investigated. Receiver operating characteristic curves (ROC) were used to study the diagnostic efficacy of CPRI, comparing against DOS and an equivalent risk index constructed using a conventional logistic regression based method with model parameters optimized to the dataset (CPRIlogistic). RESULTS: There were 42 stenosed carotid arteries with cerebrovascular symptoms, and 40 without symptoms. The presence of symptoms significantly correlated with DOS, GSM and SII (p < 0.01). The median CPRI of the symptomatic (asymptomatic) groups were 23.2 (9.2) compared with 0.71 (0.30) for CPRIlogistic (p < 0.01). The diagnostic performance of CPRI exceeded that of CPRIlogistic and DOS, and demonstrated a better separation of the symptomatic and asymptomatic groups. CONCLUSION: Our novel risk index combines quantitative measures of carotid plaque echogenicity and surface irregularities with the degree of stenosis. It is a better predictor of cerebrovascular symptoms than the degree of stenosis and could be valuable in studies and clinical trials aimed at identifying vulnerable carotid artery stenoses.

Shear Wave Elastography May Be Superior to Greyscale Median for the Identification of Carotid Plaque Vulnerability: A Comparison with Histology.

PURPOSE: There is a need to develop methods that reliably quantify characteristics associated with vulnerable carotid plaque. Greyscale median (GSM) and shear wave elastography (SWE) are two techniques that may improve individual plaque risk stratification. SWE, which quantifies Young's Modulus (YM) to estimate tissue stiffness, has been researched in the liver, breast, thyroid and prostate, but its use in carotid plaques is novel. MATERIALS AND METHODS: The aim of this study was to quantify YM and GSM of plaques and compare to histology. 25 patients (64% male) with a mean age of 76 underwent both clinical and SWE imaging. The mean GSM was quantified over a cardiac cycle. The mean YM was quantified in multiple regions within the plaque over 5 frames. Histological features were assessed following carotid endarterectomy. RESULTS: The mean YM of unstable plaques was significantly lower than that of stable plaques (50.0 kPa vs. 79.1 kPa; p = 0.027). The presence of intra-plaque hemorrhage, thrombus and increasing numbers of foam cells was also associated with a significantly lower YM. Plaque YM did not correlate well with plaque GSM (r =  .12). The mean plaque GSM was the same in both unstable and stable plaques. Fibrous plaques had a significantly higher GSM (p = 0.036). CONCLUSION: In conclusion, SWE provides additional information on plaque stiffness which may be of clinical benefit to help identify vulnerable plaque, and warrants further study.

Identification of patients with a histologically unstable carotid plaque using ultrasonic plaque image analysis.

OBJECTIVES: In patients with carotid stenosis the risk of stroke is highest in the first few days after onset of symptoms and it is low in asymptomatic patients. The ability to identify patients with a high (or low) probability of having a histologically unstable plaque might become a complimentary method that can refine the indications for surgical intervention. METHODS: Two histopathologists, using validated American Heart Association criteria, independently graded plaques harvested during carotid endarterectomy. Preoperative Duplex images were independently assessed for juxtaluminal black area, plaque type, plaque area, and grey-scale median (GSM) following image normalization. Logistic regression analysis was then performed to create a model for predicting predominantly histologically unstable or stable plaques. RESULTS: A total of 126 patients were included in the study. Based on the presence and extent of histological features including haemorrhage, thrombus, fibrous tissue, lipid core, inflammation, neovascularity, foam cells, and cap rupture, 39 plaques were graded as predominantly stable, while 87 were predominantly unstable. Unstable plaques were associated with a plaque area >95 mm(2) (OR 4.15; 95% CI 1.34-12.8 p = .009), a juxtaluminal black area >6 mm(2) (OR 2.77; 95% CI 1.24 to 6.17 p = .01) and a GSM <25 (OR 3.76; 95% CI 1.14-12.39). Logistic regression indicated that patients with the first two features had a 90% probability of having a histologically unstable plaque. The model was used to calculate the probability of having an unstable plaque in each patient. The receiver operating characteristic curve using the p value was 0.68 (95% CI 0.59-0.78). CONCLUSIONS: Computerized plaque analysis has the potential to identify patients with histologically unstable carotid plaques. This model requires validation, but offers the potential to influence patient selection for emergency interventions and the monitoring of medical therapy.

Histologically unstable asymptomatic carotid plaques have altered expression of genes involved in chemokine signalling leading to localised plaque inflammation and rupture.

BACKGROUND: Many studies have evaluated histological and gene expression profiles in TIA/stroke patients after onset of symptoms, but there is limited understanding as to how these plaque related features interact before symptom onset. In particular, no studies have evaluated differential gene expression in histologically unstable (vs stable plaques) in neurologically asymptomatic patients. METHODS: Nine asymptomatic patients had their plaques scored blindly by two independent Histopathologists using the AHA plaque scoring system. RNA extracted from the plaques was hybridised onto a whole genome microarray. Analysis was performed using GenomeStudio (v1.0) and the DAVID bioinformatics resource (v6.7). RESULTS: Three plaques were histologically unstable (Grade 2/3), while six were stable (Grade 0/1). 346 differentially expressed genes (>1.3 fold, P < 0.05) were identified (293 down-regulated and 53 up-regulated) between stable and unstable plaques. Genes related to chemokine and protein signalling (pro-inflammatory/pro-apoptotic) were identified to have high enrichment scores (>1.3) and were significantly up-regulated in unstable (asymptomatic) plaques. CONCLUSION: The findings confirm the intuitively held belief that changes in chemokine and protein signalling may be associated with acute plaque disruption and precede the onset of symptoms. Once validated, these genes could therefore become targets for innovative medical treatments in the future or could help identify asymptomatic patients with histologically unstable plaques that would benefit from surgical intervention.

Features of unstable carotid plaque during and after the hyperacute period following TIA/stroke.

BACKGROUND: The aim was to test the hypothesis that histologically unstable carotid plaque features were more prevalent in patients undergoing carotid endarterectomy (CEA) in the acute period after onset of symptoms and that the plaque would assume more stable histological characteristics as the delay from the most recent event increased. METHODS: Seven histological features of plaque instability (haemorrhage, large lipid core, chronic plaque inflammation, chronic cap inflammation, marked vascularity, cap rupture and many foam cells) were independently quantified and then correlated with recency of symptoms in patients undergoing CEA. RESULTS: In patients undergoing CEA ≤14 days of their last event, 87/119 (73%) exhibited ≥5/7 unstable histological plaque features, compared with 22/40 (55%) of patients undergoing delayed surgery (P = 0.048). As expected, there was a sustained decline in the prevalence of unstable plaque features in 61 patients undergoing surgery between days 7-28. However, there was then a marked increase in the prevalence of plaque haemorrhage (59% up to 65%), large lipid core (41% up to 78%), chronic plaque inflammation (71% up to 91%), cap rupture (35% up to 39%), many foam cells (24% up to 43%) and marked vascularity (71% up to 91%) in 23 patients undergoing CEA after 29 days had elapsed. CONCLUSION: Patients undergoing surgery ≤14 days had a significantly higher overall burden of high risk plaque features compared with those undergoing delayed CEA. However, the secondary upsurge across a range of unstable plaque features in patients undergoing CEA after ≥29 days had elapsed suggests that the relationship between recency of symptoms and plaque histology is more complex than had been anticipated in previous studies.

Dynamic cerebral autoregulation assessed by respiratory manoeuvres in non-insulin-treated Type 2 diabetes mellitus.

AIMS: This study investigated dynamic cerebral autoregulation in Type 2 diabetes, where dynamic cerebral autoregulation may be impaired as a consequence of microvascular changes and/or autonomic neuropathy. METHODS: Eleven healthy control subjects and 11 age- and sex-matched patients with Type 2 diabetes controlled with lifestyle modifications or oral anti-diabetes treatment were recruited. Dynamic cerebral autoregulation was calculated by the autoregressive moving average autoregulatory index from a continuous blood pressure and R-R interval (time between each ventricular systole) recording. End-tidal carbon dioxide was also monitored and changes in response to breath holding and hyperventilation as a metabolic stimulus were measured. RESULTS: No significant differences were seen in cerebral blood flow velocity at baseline, or in response to breath holding between people with diabetes and control subjects, although the cerebral blood flow velocity response associated with hyperventilation was significantly reduced in the diabetes group. No significant differences in dynamic cerebral autoregulation were seen at baseline or in response to respiratory manoeuvres between the groups. CONCLUSIONS: Dynamic cerebral autoregulation is not impaired in patients with Type 2 diabetes, although a small difference could not be excluded as the study was only powered to detect an autoregulatory index difference > 2 units. Further study in a larger population with a spectrum of disease severity may reveal clinically important differences.

Patients with recurrent ischaemic events from carotid artery disease have a large lipid core and low GSM.

OBJECTIVES: The aim of the current study was to determine whether computerised ultrasound plaque analysis could identify features predictive of an increased risk of early recurrent events after symptom onset. METHODS: Between August 2008 and December 2010, 158 consecutive symptomatic patients undergoing carotid endarterectomy (CEA) had their plaques harvested at CEA and then independently scored for markers of histological plaque instability. Duplex ultrasound images recorded prior to CEA were independently assessed using the Iconsoft software. RESULTS: One hundred and fifty eight recently symptomatic patients underwent CEA with 118 (75%) undergoing their operation within 14 days of their most recent clinical event. Twenty (12.7%) suffered a recurrent cerebral ischaemic event following admission to the vascular unit and before undergoing CEA. Using multivariate stepwise analysis; lipid core (OR 4.00, 95% CI 1.07 to 14.83, P = 0.042) and a low GSM (OR 6.21, 95% CI 1.86 to 20.4, P = 0.003) were independently associated with recurrent cerebrovascular events. CONCLUSION: Within a cohort of patients presenting with recent onset cerebral ischaemic events undergoing CEA, the plaques of patients with recurrent events following admission to hospital had evidence a large lipid core and a low GSM.

Rapid access carotid endarterectomy can be performed in the hyperacute period without a significant increase in procedural risks.

OBJECTIVES: The highest risk of recurrent stroke after suffering a transient ischaemic attack (TIA) or minor stroke is during the first 7-14 days. Contemporary guidelines recommend that carotid endarterectomy (CEA) should be performed within this time period, but there are concerns regarding (1) how this can be achieved logistically and (2) whether this policy is associated with a significant increase in procedural risks. DESIGN: This is a prospective, consecutive study of delays to surgery and 30-day outcomes in recently symptomatic patients who underwent CEA between 1 October 2008 and 15 June 2010 after the creation of a rapid access TIA service. RESULTS: A total of 109 symptomatic patients underwent CEA, 78% within 14 days of the index event and 90% within 14 days of referral. The median delay to surgery was 9 days from the index event and 4 days from referral. There were no perioperative deaths. Two strokes occurred (one intra-operative and one post-operative) to give a 30-day death/stroke rate of 1.83%. Patients undergoing CEA within 14 days of the index event incurred a death/stroke rate of 2.4% (2/84), increasing to 4.3% in patients undergoing surgery within 7 days (2/47). CONCLUSION: Service reconfigurations can lead to significant reductions in delays to treatment in patients with symptomatic carotid disease. CEA can be performed in the hyperacute period without significantly increasing the operative risk.

INFOMATAS multi-center systematic review and meta-analysis individual patient data of dynamic cerebral autoregulation in ischemic stroke.

RATIONALE: Disturbances in dynamic cerebral autoregulation after ischemic stroke may have important implications for prognosis. Recent meta-analyses have been hampered by heterogeneity and small samples. AIM AND/OR HYPOTHESIS: The aim of study is to undertake an individual patient data meta-analysis (IPD-MA) of dynamic cerebral autoregulation changes post-ischemic stroke and to determine a predictive model for outcome in ischemic stroke using information combined from dynamic cerebral autoregulation, clinical history, and neuroimaging. SAMPLE SIZE ESTIMATES: To detect a change of 2% between categories in modified Rankin scale requires a sample size of ∼1500 patients with moderate to severe stroke, and a change of 1 in autoregulation index requires a sample size of 45 healthy individuals (powered at 80%, α = 0.05). Pooled estimates of mean and standard deviation derived from this study will be used to inform sample size calculations for adequately powered future dynamic cerebral autoregulation studies in ischemic stroke. METHODS AND DESIGN: This is an IPD-MA as part of an international, multi-center collaboration (INFOMATAS) with three phases. Firstly, univariate analyses will be constructed for primary (modified Rankin scale) and secondary outcomes, with key co-variates and dynamic cerebral autoregulation parameters. Participants clustering from within studies will be accounted for with random effects. Secondly, dynamic cerebral autoregulation variables will be validated for diagnostic and prognostic accuracy in ischemic stroke using summary receiver operating characteristic curve analysis. Finally, the prognostic accuracy will be determined for four different models combining clinical history, neuroimaging, and dynamic cerebral autoregulation parameters. STUDY OUTCOME(S): The outcomes for this study are to determine the relationship between clinical outcome, dynamic cerebral autoregulation changes, and baseline patient demographics, to determine the diagnostic and prognostic accuracy of dynamic cerebral autoregulation parameters, and to develop a prognostic model using dynamic cerebral autoregulation in ischemic stroke. DISCUSSION: This is the first international collaboration to use IPD-MA to determine prognostic models of dynamic cerebral autoregulation for patients with ischemic stroke.

A systematic review of delays in seeking medical attention after transient ischaemic attack.

BACKGROUND: Prompt assessment and investigation of transient ischaemic attack (TIA) followed by early initiation of secondary prevention is effective in reducing recurrent stroke. Nevertheless, many patients are slow to seek medical advice after TIA. A systematic review was undertaken to examine potential factors associated with delay in seeking medical review after TIA. METHODS: The electronic databases MEDLINE, EMBASE, and Science Citation Index were searched for observational studies assessing patient delay in presentation after TIA. The search was restricted to studies published between December 1995 and September 2008. RESULTS: The electronic search yielded nine studies with data on presentation delay in patients with TIA; variations existed in study size, population and methodology. One study included patients with TIA only (n = 241), whereas the remaining eight studies recruited both stroke and TIA patients. Overall, TIA patients (n = 821) made up only a small proportion of the total number of patients in this analysis (n = 3,202). Length of delay varied greatly across all studies. In most studies, patients with TIA who attended an emergency department arrived there within hours. Where patients first presented to their general practitioner, 50% attended within 24 hours whereas 25% waited 2 days or more. Recognition of symptoms as stroke/TIA did not reduce the delay. CONCLUSIONS: The majority of delay in seeking assessment after TIA is due to a lack of response by the patient-many patients do not recognise the symptoms of stroke/TIA, and even when they do, many fail to seek emergency medical attention. The public needs educating on the importance of contacting the emergency medical services or attending an emergency department immediately after TIA.