von Willebrand factor antigen, von Willebrand factor propeptide and ADAMTS13 activity in TIA or ischaemic stroke patients changing antiplatelet therapy.

Data are limited on the impact of commencing antiplatelet therapy on von Willebrand Factor Antigen (VWF:Ag) or von Willebrand Factor propeptide (VWFpp) levels and ADAMTS13 activity, and their relationship with platelet reactivity following TIA/ischaemic stroke. In this pilot, observational study, VWF:Ag and VWFpp levels and ADAMTS13 activity were quantified in 48 patients ≤4 weeks of TIA/ischaemic stroke (baseline), and 14 days (14d) and 90 days (90d) after commencing aspirin, clopidogrel or aspirin+dipyridamole. Platelet reactivity was assessed at moderately-high shear stress (PFA-100® Collagen-Epinephrine / Collagen-ADP / INNOVANCE PFA P2Y assays), and low shear stress (VerifyNow® Aspirin / P2Y12, and Multiplate® Aspirin / ADP assays). VWF:Ag levels decreased and VWFpp/VWF:Ag ratio increased between baseline and 14d and 90d in the overall population (P ≤ 0.03). In the clopidogrel subgroup, VWF:Ag levels decreased and VWFpp/VWF:Ag ratio increased between baseline and 14d and 90d (P ≤ 0.01), with an increase in ADAMTS13 activity between baseline vs. 90d (P ≤ 0.03). In the aspirin+dipyridamole subgroup, there was an inverse relationship between VWF:Ag and VWFpp levels with both PFA-100 C-ADP and INNOVANCE PFA P2Y closure times (CTs) at baseline (P ≤ 0.02), with PFA-100 C-ADP, INNOVANCE PFA P2Y and C-EPI CTs at 14d (P ≤ 0.05), and between VWF:Ag levels and PFA-100 INNOVANCE PFA P2Y CTs at 90d (P = 0.03). There was a positive relationship between ADAMTS13 activity and PFA-100 C-ADP CTs at baseline (R2 = 0.254; P = 0.04). Commencing/altering antiplatelet therapy, mainly attributed to commencing clopidogrel in this study, was associated with decreasing endothelial activation following TIA/ischaemic stroke. These data enhance our understanding of the impact of VWF:Ag and VWFpp especially on ex-vivo platelet reactivity status at high shear stress after TIA/ischaemic stroke.

Assessment of on-treatment platelet reactivity at high and low shear stress and platelet activation status after the addition of dipyridamole to aspirin in the early and late phases after TIA and ischaemic stroke.

BACKGROUND: Data are limited on the ability of dipyridamole to additionally inhibit platelet function/reactivity in ischaemic cerebrovascular disease (CVD) patients on aspirin. AIMS: To assess inhibition of platelet function/reactivity and platelet activation with dipyridamole in CVD. METHODS: This prospective, observational study assessed TIA/ischaemic stroke patients before (baseline; N = 60), at 14 ±7 days (14d, N = 39) and ≥ 90 days (90d, N = 31) after adding dipyridamole to aspirin. Platelet function/reactivity at high shear stress (PFA-100® C-ADP) and low shear stress (VerifyNow® P2Y12 and Multiplate® ADP assays), and platelet activation status (% expression of CD62P, CD63 and leucocyte-platelet complexes on whole blood flow cytometry) were quantified. 'Dipyridamole-high on-treatment platelet reactivity (HTPR)' was defined as failure to inhibit ADP-induced platelet aggregation +/- adhesion compared with the patient's baseline on aspirin monotherapy by more than twice the coefficient-of-variation of the assay after adding dipyridamole to aspirin. RESULTS: Dipyridamole-HTPR was identified in 71.4-75% of patients on PFA-100 C-ADP, 83.9-86.8% of patients on VerifyNow P2Y12, and 81.5-83.3% of patients on Multiplate ADP assays. There were no changes in CD62P/CD63 expression (P ≥ 0.18), or consistent changes in leucocyte-platelet complexes in CVD patients overall at 14d or 90d vs. baseline after commencing dipyridamole. Monocyte-platelet complexes increased in the patient subgroup with dipyridamole-HTPR at 14d and 90d on PFA-100, and at 14d on VerifyNow (P ≤ 0.04), but not in those without dipyridamole-HTPR. DISCUSSION: Additional antiplatelet effects of dipyridamole are detectable under high and low shear stress conditions with user-friendly platelet function/reactivity tests ex vivo. Increasing circulating monocyte-platelet complexes over time are associated with dipyridamole-HTPR.

Discharge destination after hip fracture: findings from the Irish hip fracture database.

PURPOSE: Although home continues to be the place from which the majority of patients are admitted, less than one third of patients are Discharged Directly Home (DDH) following hip fracture. Once ready for discharge, DDH as opposed to Discharge to an Alternative Location (DAL), i.e., community care, rehabilitation facility or long-term care, is a high priority for patients and clinicians alike. Not only is DDH integral to the quality of life of patients, it is also an essential driver of the socioeconomic cost of hip fracture care. METHODS: We analysed 21,819 cases in the Irish Hip Fracture Database from 2013 to 2019. Descriptive and analytical statistics were conducted. RESULTS: 29% (n = 6476) of patients were DDH during the study period. On multivariate analysis, the odds of DDH decreased as age increased (OR 0.28, p < 0.01, 95% CI 0.24-0.34). Patients who were independently mobile prior to fracture were 47% more likely to be DDH (OR 1.47, p < 0.01, 95% CI 1.29-1.68). Those mobilised early post operatively were 24% more likely to be DDH (OR 1.24, p < 0.01, 95% CI 1.06-1.45). Patients who waited > 72 h prior to surgery were 30% less likely to be DDH (OR 0.70, p < 0.01, 95% CI 0.56-0.88). CONCLUSION: The authors identified patient characteristics that increased the likelihood of DDH, i.e., younger patients independently mobile prior to fracture, who received timely surgery and early post-operative mobilisation. The Irish Hip Fracture Standards (IHFS) incorporate 2 out the 3 modifiable factors identified, which reinforces the importance of the IHFS in improving patient outcomes.

Profile of reticulated platelets in the early, subacute and late phases after transient ischemic attack or ischemic stroke.

Information regarding the profile of reticulated platelets (RP) in ischemic cerebrovascular disease (CVD) patients is limited. Data from two prospective, observational, case-control studies were combined to compare the %RP using whole blood flow cytometry in patients ≤ 4 weeks of TIA/stroke onset (baseline, N = 210), and 14 ±7 days (14d, N = 182) and ≥ 90 days (90d, N = 145) after starting or changing antiplatelet therapy with healthy controls (N = 34). There were no differences in median %RP between the overall CVD patient population at baseline or 14d vs. controls (P ≥ 0.2). However, the median %RP was significantly higher in CVD patients overall at 90d (P = .036), and in the subgroup of patients with "lacunar" TIA/ischemic stroke at baseline (P = .04) and at 90d (P = .01), but not at 14d (P = .06) vs. controls. There were no significant differences in the median %RP between other TIA/stroke subgroups and controls (P ≥ 0.05). Elevated circulating reticulated platelets, as a marker of increased platelet production/turnover, may occur following an ischemic event in a well-phenotyped TIA/ischemic stroke population overall, but may precede symptom onset at least in the subgroup with small vessel occlusion. These data improve our understanding of the profile of reticulated platelets in CVD patients.

Characteristics of Centenarians in the Irish Hip Fracture Database.

Aim Hip fractures are common amongst older people and result in significant morbidity and mortality. The Irish Hip Fracture Database (IHFD) collects data, from the 16 trauma orthopaedic units in Ireland, on patients aged 60 years and older who sustain hip fractures. This study aims to describe the characteristics of those patients aged 100 years and older in this database. Methods A retrospective analysis of the IHFD from 2012 to 2017. Characteristics of those patients aged 100 years and over were collected and analysed. Results 57 patients were identified for inclusion, 52 (91%) of which were women. Mean age was 101, while mean length of stay was 22.6 days. 51 (89%) fractures were due to low velocity trauma, consistent with likely high rates of osteoporosis in this group. The great majority underwent operative intervention. 50 (88%) were discharged alive. Fracture type varied widely. Only 24 (42%) patients were documented to have been seen by a geriatrician during admission. There were low reported rates of co-morbid medical conditions, likely due to lack of recorded data, rather than true low rates of co-morbidities in this group. Discussion This study provides insight into this distinct group of people, with important implications for future healthcare planning and budgeting.

Trends in hip fracture care in the Republic of Ireland from 2013 to 2018: results from the Irish Hip Fracture Database.

Hip fractures continue to be one of the most serious and costly injuries suffered by older people globally. This paper describes the development of a national hip fracture audit and summarises the first 6 years of data from the Republic of Ireland. This can help inform care, standards and outcomes of hip fracture patients. INTRODUCTION: Ireland has one of the highest standardised rates of hip fracture in the world behind northern European countries. The Irish Hip Fracture Database (IHFD) was established in 2012 to drive clinical and organisational improvements in quality and effectiveness of hip fracture care. This paper describes the progression of the IHFD between 2013 and 2018 and identifies trends and areas for improvement. METHODS: The IHFD is a clinically led, web-based audit, with data collected through the national Hospital Inpatient Enquiry (HIPE) electronic system, the principal source of information from publicly funded acute hospitals in Ireland. Eligible cases are aged ≥ 60 years with hip fracture as defined by IHFD or with other specified hip fracture excluding periprosthetic fractures. As of 2015, all 16 trauma-receiving hospitals within Ireland submitted data. Demographics and adherence to six national quality standards are described. RESULTS: A total of 17,983 cases were included in the analysis. National coverage has increased from 63% in 2013 to 99% in 2018. Demographic characteristics are unchanged, but higher levels of comorbidity are seen. Internal fixation and hemiarthroplasty are the most common modes of surgical repair with two-thirds of cases receiving spinal rather than general anaesthesia. Increasingly patients are being assessed by a geriatrician (11% in 2013 to 69% in 2018) and receive a bone health assessment (65% in 2013 to 84% in 2018). CONCLUSION: While some hip fracture standards have improved, further improvements are required to compare favourably internationally. Reduction of surgical delay and ensuring early mobilisation post-operatively are immediate priorities for the IHFD.

Relationship between 'on-treatment platelet reactivity', shear stress, and micro-embolic signals in asymptomatic and symptomatic carotid stenosis.

BACKGROUND: Assessment of 'high on-treatment platelet reactivity (HTPR)' could enhance understanding of the pathophysiology of first or recurrent vascular events in carotid stenosis patients on antiplatelet therapy. METHODS: This prospective, multi-centre study assessed antiplatelet-HTPR status and its relationship with micro-emboli signals (MES) in asymptomatic vs. symptomatic ≥ 50-99% carotid stenosis. Platelet function/reactivity was assessed under 'moderately high shear stress' with the PFA-100® and 'low shear stress' with VerifyNow® and Multiplate® analysers. Bilateral 1-h transcranial Doppler ultrasound of the middle cerebral arteries classified patients as MES + ve or MES - ve. RESULTS: Data from 34 asymptomatic patients were compared with 43 symptomatic patients in the 'early phase' (≤ 4 weeks) and 37 patients in the 'late phase' (≥ 3 months) after TIA/ischaemic stroke. Median daily aspirin doses were higher in early symptomatic (225 mg; P < 0.001), but not late symptomatic (75 mg; P = 0.62) vs. asymptomatic patients (75 mg). There was a lower prevalence of aspirin-HTPR in early (28.6%; P = 0.028), but not late symptomatic (38.9%; P = 0.22) compared with asymptomatic patients (56.7%) on the PFA-100®, but not on the VerifyNow® or Multiplate® (P ≤ 0.53). Early symptomatic patients had a higher prevalence of aspirin-HTPR on the PFA-100® (28.6%) vs. VerifyNow® (9.5%; P = 0.049), but not Multiplate® assays (11.9%, P = 0.10). There was no difference in aspirin-HTPR prevalence between any symptomatic vs. asymptomatic MES + ve or MES - ve subgroup. DISCUSSION: Recently symptomatic moderate-severe carotid stenosis patients had a lower prevalence of aspirin-HTPR than their asymptomatic counterparts on the PFA-100®, likely related to higher aspirin doses. The prevalence of antiplatelet-HTPR was positively influenced by higher shear stress levels, but not MES status.

Patterns of mortality in modern stroke care

Background Stroke is a leading cause of death. We looked at the causes (direct and indirect) of in-hospital mortality in a modern stroke unit over a two-year period. Methods We reviewed medical charts of stroke deaths in hospital from 2014-2015 inclusive. Data on stroke type, aetiology, age, length of stay, comorbidities, and documented cause of death were recorded. All patients were included. Results 518 patients were admitted acutely to the stroke service. Overall death rate was 7.5% (n=39). Of fatal strokes 29 (74%) were ischaemic. Average age 78.6 years. Mean survival was 26.4 days (range 1-154). 19 (49%) patients had atrial fibrillation. Forty-nine percent of deaths were due to pneumonia, and 33% were due to raised intracranial pressure. Discussion Mortality rate in our stroke service has decreased from 15% in 1997, and now appears dichotomised into early Secondary Stroke Related Cerebral Events (SSRCEs) and later infections.

Screening for frailty in older emergency department patients: the utility of the Survey of Health, Ageing and Retirement in Europe Frailty Instrument.

BACKGROUND: Greater numbers of older patients are accessing hospital services. Specialist geriatric input at presentation may improve outcomes for at-risk patients. The Survey of Health, Ageing and Retirement in Europe Frailty Instrument (SHARE-FI) frailty measure, developed for use in the community, has also been used in the emergency department (ED). AIM: To measure frailty, review its prevalence in older patients presenting to ED and compare characteristics and outcomes of frail patients with their non-frail counterparts. DESIGN: Patient characteristics were recorded using symphony® electronic data systems. SHARE-FI assessed frailty. Cognition, delirium and 6 and 12 months outcomes were reviewed. METHODS: A prospective cohort study was completed of those aged ≥70 presenting to ED over 24 h, 7 days a week. RESULTS: Almost half of 198 participants (46.7%, 93/198) were classified as frail, but this was not associated with a significant difference in mortality rates (OR 0.89, 95% CI 0.58-1.38, P = 0.614) or being alive at home at 12 months (OR 1.07, 95% CI 0.72-1.57, P = 0.745). Older patients were more likely to die (OR 2.34, 95% CI 1.30-4.21, P = 0.004) and less likely to be alive at home at 12 months (OR 0.49, 95% CI 0.23-0.83, P = 0.009). Patients with dementia (OR 0.24, P = 0.005) and on ≥5 medications (OR 0.37, 95% CI 0.16-0.87, P = 0.022) had a lower likelihood of being alive at home at 12 months. CONCLUSIONS: Almost half of the sample cohort was frail. Older age was a better predictor of adverse outcomes than frailty as categorized by the SHARE-FI. SHARE-FI has limited predictability when used as a frailty screening instrument in the ED.

Investigation and diagnostic formulation in patients admitted with transient loss of consciousness.

Several commonly completed tests have low diagnostic yield in the setting of transient loss of consciousness (T-LOC). We estimated the use and cost of inappropriate investigations in patients admitted with T-LOC and assessed if these patients were given a definitive diagnosis for their presentation. We identified 80 consecutive patients admitted with T-LOC to a university teaching hospital. Eighty-eight percent (70/80) had a computerized topography (CT) brain scan and 49% (34/70) of these scans were inappropriate based on standard guidelines. Almost half (17/80) of electroencephalograms (EEG) and 82% (9/11) of carotid doppler ultrasound performed were not based on clinical evidence of seizure or stroke respectively. Forty-four percent (35/80) of patients had no formal diagnosis documented for their presentation. Inappropriate investigation in T-LOC is very prevalent in the acute hospital, increasing cost of patient care. In addition, there is poor diagnostic formulation for T-LOC making recurrent events more likely in the absence of definitive diagnoses.

Profile of von Willebrand factor antigen and von Willebrand factor propeptide in an overall TIA and ischaemic stroke population and amongst subtypes.

INTRODUCTION: Von Willebrand factor propeptide (VWF:Ag II) is proposed to be a more sensitive marker of acute endothelial activation than von Willebrand factor antigen (VWF:Ag). Simultaneous data on VWF:Ag and VWF:Ag II profiles are very limited following TIA and ischaemic stroke. METHODS: In this prospective, observational, case-control study, plasma VWF:Ag and VWF:Ag II levels were quantified in 164 patients≤4weeks of TIA or ischaemic stroke (baseline), and then ≥14days (14d) and ≥90days (90d) later, and compared with those from 27 healthy controls. TIA and stroke subtyping was performed according to the TOAST classification. The relationship between VWF:Ag and VWF:Ag II levels and platelet activation status was assessed. RESULTS: 'Unadjusted' VWF:Ag and VWF:Ag II levels were higher in patients at baseline, 14d and 90d than in controls (p≤0.03). VWF:Ag levels remained higher in patients than controls at baseline (p≤0.03), but not at 14d or 90d after controlling for differences in age or hypertension, and were higher in patients at baseline and 90d after controlling for smoking status (p≤0.04). 'Adjusted' VWF:Ag II levels were not higher in patients than controls after controlling for age, hypertension or smoking (p≥0.1). Patients with symptomatic carotid stenosis (N=46) had higher VWF:Ag and VWF:Ag II levels than controls at all time-points (p≤0.002). There was no significant correlation between platelet activation status and VWF:Ag or VWF:Ag II levels. CONCLUSIONS: VWF:Ag and VWF:Ag II levels are increased in an overall TIA and ischaemic stroke population, especially in patients with recently symptomatic carotid stenosis. VWF:Ag II was not superior to VWF:Ag at detecting acute endothelial activation in this cohort and might reflect timing of blood sampling in our study.

Dementia in the acute hospital: the prevalence and clinical outcomes of acutely unwell patients with dementia.

BACKGROUND: Studies have demonstrated that a significant minority of older persons presenting to acute hospital services are cognitively impaired; however, the impact of dementia on long-term outcomes is less clear. AIM: To evaluate the prevalence of dementia, both formally diagnosed and hitherto unrecognised in a cohort of acutely unwell older adults, as well as its impact on both immediate outcomes (length of stay and in-hospital mortality) and 12-month outcomes including readmission, institutionalisation and death. DESIGN: Prospective observational study. METHODS: 190 patients aged 70 years and over, presenting to acute hospital services underwent a detailed health assessment including cognitive assessment (standardised Mini Mental State Examination, AD8 and Confusion Assessment Method for the Intensive Care Unit). Patients or informants were contacted directly 12 months later to compile 1-year outcome data. Dementia was defined as a score of 2 or more on the AD8 screening test. RESULTS: Dementia was present in over one-third of patients (73/190). Of these patients, 36% (26/73) had a prior documented diagnosis of dementia with the remaining undiagnosed before presentation. The composite outcome of death or readmission to hospital within the following 12 months was more likely to occur in patients with dementia (73% (53/73) vs. 58% (68/117), P = 0.043). This finding persisted after controlling for age, gender, frailty status and medical comorbidities, including stroke and heart disease. CONCLUSION: A diagnosis of dementia confers an increased risk of either death or further admission within the following 12 months, highlighting the need for better cognitive screening in the acute setting, as well as targeted intervention such as comprehensive geriatric assessment.

Acute hospital care: how much activity is attributable to caring for patients with dementia?

BACKGROUND: People with dementia are among the most frequent service users in the acute hospital. Despite this, the acute hospital is not organized in a manner that best addresses their needs. METHODS: We examined acute dementia care over a 3-year period from 2010 to 2012 in a 600-bed university hospital, to clarify the service activity and costs attributable to acute dementia care. RESULTS: Nine hundred and twenty-nine patients with dementia were admitted during the study period, accounting for 1433/69 718 (2%) of all inpatient episodes, comprising 44 449/454 169 (10%) of total bed days. The average length of stay was 31.0 days in the dementia group and 14.1 days in those >65 years without dementia. The average hospital care cost was almost three times more (€13 832) per patient with dementia, compared with (€5404) non-dementia patients, accounting for 5% (almost €20 000 000) of the total hospital casemix budget for the period. DISCUSSION: Service activity attributable to dementia care in the acute hospital is considerable. Moreover, given the fact that a significant minority of cognitive impairment goes unrecognized after acute admissions, it is likely that this is under-representative of the full impact of dementia in acute care. Although the money currently being spent on acute dementia care is considerable, it is being used to provide a service that does not meet its user needs adequately. It is clear that acute hospitals need to provide a more 'dementia friendly' service for acutely unwell older persons.

Characteristics and Outcomes of Older Patients Attending an Acute Medical Assessment Unit.

The care of older persons accounts for an increasing proportion of the unscheduled care workload for acute hospitals. The recent development of acute medical assessment units (AMAU) has provided an alternative model for acute unscheduled care for all medical patients. Screening instruments have been developed to capture the higher levels of clinical complexity and medical comorbidities that older patients present with. The aim of this study was to report on the characteristics and outcomes for older patients reviewed in the AMAU of a tertiary referral university teaching hospital. Data on 3071 patients attending the unit over one year was prospectively collected and information on characteristics and outcomes for older patients retrieved. Older patients represented over one third (1066/3071, 35%) of those attending AMAU, and had an admission rate of nearly twice that of younger patients (60.5% vs 32%), highlighting the increased complexity of this group. Gerontologically attuned AMAUs have great potential to enhance care for frail older patients from the time of their acute presentation to hospital.

Added Value of Stroke Protocol MRI Following Negative Initial CT in the Acute Stroke Setting.

The aim of the study was to determine the added value of stroke protocol MRI following negative initial CT brain in the acute stroke setting. A retrospective study was performed over a 6 month period in a tertiary referral stroke centre. Patients were selected from the stroke and radiology databases. Inclusion criteria: clinical stroke syndrome, negative initial CT with subsequent MRI study with diffusion weighted sequences. Ninety two patients were reviewed and 73 (M:F of 39:34, mean age 62.1 ± 14.0 years) met the inclusion criteria. Twenty MRI studies (27.4%) were positive for acute/subacute ischaemia in the setting of a normal initial CT. The average time interval between initial CT and MRI brain imaging was 4.7 ± 2.6 days. Whilst CT continues to be the first line imaging investigation for acute stroke, MRI has substantial added value following negative initial CT in the diagnosis of stroke.

Increased thrombin generation potential in symptomatic versus asymptomatic moderate or severe carotid stenosis and relationship with cerebral microemboli.

INTRODUCTION: The importance of thrombin generation in the pathogenesis of TIA or stroke and its relationship with cerebral microembolic signals (MES) in asymptomatic and symptomatic carotid stenosis has not been comprehensively assessed. METHODS: Plasma thrombin generation parameters from patients with moderate or severe (≥ 50%) asymptomatic carotid stenosis were compared with those from patients with symptomatic carotid stenosis in the early (≤ 4 weeks) and late phases (≥ 3 months) after TIA or stroke in this prospective, pilot observational study. Thrombin generation profile was longitudinally assessed in symptomatic patients with data at each time point. Bilateral transcranial Doppler ultrasound monitoring of the middle cerebral arteries was performed whenever possible to classify patients as MES-positive or MES-negative. RESULTS: Data from 31 asymptomatic, 46 'early symptomatic' and 35 'late symptomatic' patients were analysed. Peak thrombin (344.2 nM vs 305.3 nM; p = 0.01) and endogenous thrombin potential (1772.4 vs 1589.7; p = 0.047) were higher in early symptomatic than asymptomatic patients. Peak thrombin production decreased in symptomatic patients followed up from the early to late phase after TIA or stroke (339.7 nM vs 308.6 nM; p = 0.02). Transcranial Doppler ultrasound data were available in 25 asymptomatic, 31 early symptomatic and 27 late symptomatic patients. Early symptomatic MES-positive patients had a shorter 'time-to-peak thrombin' than asymptomatic MES-positive patients (p=0.04), suggesting a more procoagulant state in this early symptomatic subgroup. DISCUSSION: Thrombin generation potential is greater in patients with recently symptomatic than asymptomatic carotid stenosis, and decreases over time following TIA or stroke associated with carotid stenosis. These data improve our understanding of the haemostatic/thrombotic biomarker profile in moderate-severe carotid stenosis.

Characteristics and outcomes of older persons attending the emergency department: a retrospective cohort study.

BACKGROUND: The analysis of routinely collected hospital data informs the design of specialist services for at-risk older people. AIM: Describe the outcomes of a cohort of older emergency department (ED) attendees and identify predictors of these outcomes. DESIGN: retrospective cohort study. METHODS: All patients aged 65 years or older attending an urban university hospital ED in January 2012 were included (N = 550). Outcomes were retrospectively followed for 12 months. Statistical analyses were based on multivariate binary logistic regression models and classification trees. RESULTS: Of N = 550, 40.5% spent ≤6 h in the ED, but the proportion was 22.4% among those older than 81 years and not presenting with musculoskeletal problems/fractures. N = 349 (63.5%) were admitted from the ED. A significant multivariate predictor of in-hospital mortality was Charlson comorbidity index [CCI; odds ratio = 1.19, 95% confidence interval: 1.07, 1.34, P = 0.002]. Among patients who were discharged from ED without admission or after their first in-patient admission (N = 499), 232 (46.5%) re-attended ED within 1 year, with CCI being the best predictor of re-attendance (CCI ≤ 4: 25.8%, CCI > 5: 60.4%). Among N = 499, 34 (6.8%) had died after 1 year of initial ED presentation. The subgroup (N = 114) with the highest mortality (17.5%) was composed by those aged >77 years and brought in by ambulance on initial presentation. CONCLUSIONS: Advanced age and comorbidity are important drivers of outcomes among older ED attendees. There is a need to embed specialist geriatric services within frontline services to make them more gerontologically attuned. Our results predate the opening of an acute medical unit with specialist geriatric input.

Longitudinal assessment of von Willebrand factor antigen and von Willebrand factor propeptide in response to alteration of antiplatelet therapy after TIA or ischaemic stroke.

The impact of commencing or changing antiplatelet therapy on von Willebrand factor antigen (VWF:Ag) and von Willebrand factor propeptide (VWF:Ag II) levels has not been comprehensively assessed following TIA or ischaemic stroke. In this pilot, longitudinal, observational analytical study, VWF:Ag and VWF:Ag II levels were simultaneously quantified in platelet poor plasma by ELISA in patients within 4 weeks of TIA or ischaemic stroke (baseline), and then 14 days (14d) and >90 days (90d) after altering antiplatelet therapy. Ninety-one patients were recruited. Eighteen were initially assessed on no antiplatelet therapy, and then after 14d (N = 17) and 90d (N = 8) on aspirin monotherapy; 21 patients were assessed on aspirin and after 14d and 90d on clopidogrel; 52 were assessed on aspirin monotherapy, and after 14d and 90d on aspirin and dipyridamole combination therapy. VWF:Ag, VWF:Ag II levels and VWF:Ag/VWF:Ag II ratio were unchanged at 14d and 90d in the overall study population (p ≥ 0.1). VWF:Ag and VWF:Ag II levels remained stable at 14d and 90d after commencing aspirin (p ≥ 0.054), and after changing from aspirin to clopidogrel (p ≥ 0.2). Following the addition of dipyridamole MR to aspirin, there was a significant reduction in VWF:Ag levels at 14d (p = 0.03) and 90d (p = 0.005), but not in VWF:Ag II levels (p ≥ 0.3). The addition of dipyridamole to aspirin led to a persistent reduction in VWF:Ag but not in VWF:Ag II levels, suggesting that dipyridamole may inhibit release of platelet-derived VWF:Ag following TIA or ischaemic stroke.

Increased endothelial activation in recently symptomatic versus asymptomatic carotid artery stenosis and in cerebral microembolic-signal-negative patient subgroups.

BACKGROUND AND PURPOSE: von Willebrand factor propeptide (VWF:Ag II) is potentially a more sensitive marker of acute endothelial activation than von Willebrand factor antigen (VWF:Ag). These biomarkers have not been simultaneously assessed in asymptomatic versus symptomatic carotid stenosis patients. The relationship between endothelial activation and cerebral microembolic signals (MESs) detected on transcranial Doppler ultrasound is unknown. METHODS: In this multicentre observational analytical study, plasma VWF:Ag and VWF:Ag II levels in patients with ≥50% asymptomatic carotid stenosis were compared with those from patients with ≥50% symptomatic carotid stenosis in the 'early' (≤4 weeks) and 'late' (≥3 months) phases after transient ischaemic attack or ischaemic stroke. Endothelial activation was also longitudinally assessed in symptomatic patients during follow-up. Transcranial Doppler ultrasound monitoring classified patients as MES-positive or MES-negative. RESULTS: Data from 31 asymptomatic patients were compared with those from 46 early symptomatic and 35 late phase symptomatic carotid stenosis patients, 23 of whom had undergone carotid intervention. VWF:Ag II levels were higher in early (12.8 µg/ml; P < 0.001), late (10.6 µg/ml; P = 0.01) and late post-intervention (10.6 µg/ml; P = 0.038) symptomatic patients than asymptomatic patients (8.9 µg/ml). VWF:Ag levels decreased in symptomatic patients followed up from the early to late phase after symptom onset (P = 0.048). Early symptomatic MES-negative patients had higher VWF: Ag II levels (13.3 vs. 9.0 µg/ml; P < 0.001) than asymptomatic MES-negative patients. CONCLUSIONS: Endothelial activation is enhanced in symptomatic versus asymptomatic carotid stenosis patients, in early symptomatic versus asymptomatic MES-negative patients, and decreases over time in symptomatic patients. VWF:Ag II levels are a more sensitive marker of endothelial activation than VWF:Ag levels in carotid stenosis. The potential value of endothelial biomarkers and concurrent cerebral MES detection at predicting stroke risk in carotid stenosis warrants further study.