Dose-Dependent Association of Inflammatory Cytokines with Carotid Atherosclerosis in Transient Ischaemic Attack: Implications for Clinical Trials.

INTRODUCTION: The 5-year recurrence risk after ischaemic stroke and transient ischaemic attack (TIA) is 25-30%. Although inflammation may be a target for prevention trials, the contribution of plaque inflammation to acute cerebrovascular events remains unclear. We investigated the association of acute inflammatory cytokines and high-sensitivity C-reactive protein (CRP) with recently symptomatic carotid atherosclerosis in a prospective cohort study. METHODS: Blood and Imaging markers of TIA BIO-TIA) is a multicentre prospective study of imaging and inflammatory markers in patients with TIA. Exclusion criteria were infection and other co-morbid illnesses associated with inflammation. CRP and serum cytokines (interleukin [IL]-6, IL-1ß, IL-8, IL-10, IL-12, interferon-γ [IFN-γ] and tumour necrosis factor-α [TNF-α]) were measured. All patients had carotid imaging. RESULTS: Two hundred and thirty-eight TIA cases and 64 controls (TIA mimics) were included. Forty-nine (20.6%) cases had symptomatic internal carotid artery stenosis. Pro-inflammatory cytokine levels increased in a dose-dependent manner across controls, TIA without carotid stenosis (CS), and TIA with CS (IL-1ß, ptrend = 0.03; IL-6, ptrend < 0.0001; IL-8, ptrend = 0.01; interferon (IFN)-γ, ptrend = 0.005; TNF-α, ptrend = 0.003). Results were unchanged when DWI-positive cases were excluded. On multivariable linear regression, only age (p = 0.01) and CS (p = 0.04) independently predicted log-IL-6. On multivariable Cox regression, CRP was the only independent predictor of 90-day stroke recurrence (adjusted hazard ratio per 1-unit increase 1.03 [95% CI: 1.01-1.05], p = 0.003). CONCLUSION: Symptomatic carotid atherosclerosis was associated with elevated cytokines in TIA patients after controlling for other sources of inflammation. High-sensitivity CRP was associated with recurrent ischaemic stroke at 90 days. These findings implicate acute plaque inflammation in the pathogenesis of cerebral thromboembolism and support a rationale for randomized trials of anti-inflammatory therapy for stroke patients, who were excluded from coronary trials.

The association between increasing oral anticoagulant prescribing and atrial fibrillation related stroke in Ireland.

AIMS: Recent increases in the number of patients with atrial fibrillation (AF) prescribed oral anticoagulants (OAC) are evident in Ireland and internationally, largely due to the availability of direct oral anticoagulants (DOACs). This study aimed to determine the rate of stroke in the context of increasing anticoagulation utilisation, with a focus on AF-related ischaemic stroke (IS). METHODS: Dispensing data for OACs were identified for the period 2010-2018 as well as hospital discharges for IS (2005-2018). Irish National Stroke Register data were used to elucidate the characteristics of patients with acute ischaemic stroke. RESULTS: The number of patients prescribed OACs increased by 94% from 2010-2018 with a significant change from 2013 (ß = 2.57, P = .038), associated with a large increase in the number of patients on DOACs. There was 3.3-fold increase in expenditure on OACs nationally from 2013 to 2018, of which 94% was DOAC related. Using the 2013 timepoint, ischaemic stroke rates until 2018 did not show a significant deviation from the previous trend (ß = 0.00, P = .898). The percentage of AF-related ischaemic stroke was stable from 2013 to 2017 with a 4.5% decrease in 2018. The percentage of ischaemic stroke patients with previously diagnosed AF decreased from 2013 to 2018; however, there was an increase in the percentage of ischaemic strokes while on OAC in this cohort. CONCLUSION: Large increases in OAC utilisation have not resulted in changes in ischaemic stroke rates at a national level. The percentage of ischaemic strokes with a previous diagnosis of AF has decreased indicating a possible benefit from greater OAC utilisation. However, the percentage presenting with an ischaemic stroke while on OAC treatment is increasing. The increase in patients presenting with stroke while treated with OAC may largely reflect the national increase in patients prescribed DOACs but the findings raise concerns about treatment failures. The real-world effectiveness of DOACs requires further examination.

Early repatriation post-thrombectomy: a model of care which maximises the capacity of a stroke network to treat patients with large vessel ischaemic stroke.

BACKGROUND AND PURPOSE: Healthcare systems are challenged to provide access to thrombectomy in acute stroke patients. Either the "drip and ship" or "mothership" models result in increased numbers of patients in the endovascular stroke centre (ESC). We describe our approach for a "drip, ship, retrieve and leave" model repatriating patients immediately or within 24 hours of thrombectomy. METHODS: We included consecutive patients who underwent thrombectomy from January 2016 to June 2018. Patients from local region primary stroke centres (PSC) are immediately repatriated and those from remote region PSCs are admitted for 24 hours before repatriation. Key parameters recorded included clinical, radiological and timeline data as well as 90-day modified Rankin Scale (mRS). Patients who stayed beyond the intended time period in the ESC were analysed. RESULTS: From January 2016 to June 2018, 435 patients were transferred, with 352 patients in the local region group and 83 in the remote region group. The median NIHSS was 16 with a median ASPECTS of 9. Good functional outcome was seen in 47% of patients with a mortality rate of 19%. The local region group that were repatriated at the intended time period had a 90-day mRS 0-2 of 47% compared with 20% of those admitted to the ESC (P=0.006). Mortality rates were 20% and 27% respectively (P=0.377). The remote region group, repatriated at 24 hours' post-emergency endovascular thrombectomy had 90-day mRS 0-2 of 65% compared with 41% in the group admitted (P=0.042). Mortality rates were 4% and 22% respectively (P=0.007). CONCLUSION: This model enables the treatment of large numbers of patients with large vessel occlusion acute ischaemic stroke with thrombectomy within a national stroke service and system of care which would not otherwise be facilitated.

Investigating post-stroke fatigue: An individual participant data meta-analysis.

OBJECTIVE: The prevalence of post-stroke fatigue differs widely across studies, and reasons for such divergence are unclear. We aimed to collate individual data on post-stroke fatigue from multiple studies to facilitate high-powered meta-analysis, thus increasing our understanding of this complex phenomenon. METHODS: We conducted an Individual Participant Data (IPD) meta-analysis on post-stroke fatigue and its associated factors. The starting point was our 2016 systematic review and meta-analysis of post-stroke fatigue prevalence, which included 24 studies that used the Fatigue Severity Scale (FSS). Study authors were asked to provide anonymised raw data on the following pre-identified variables: (i) FSS score, (ii) age, (iii) sex, (iv) time post-stroke, (v) depressive symptoms, (vi) stroke severity, (vii) disability, and (viii) stroke type. Linear regression analyses with FSS total score as the dependent variable, clustered by study, were conducted. RESULTS: We obtained data from 14 of the 24 studies, and 12 datasets were suitable for IPD meta-analysis (total n = 2102). Higher levels of fatigue were independently associated with female sex (coeff. = 2.13, 95% CI 0.44-3.82, p = 0.023), depressive symptoms (coeff. = 7.90, 95% CI 1.76-14.04, p = 0.021), longer time since stroke (coeff. = 10.38, 95% CI 4.35-16.41, p = 0.007) and greater disability (coeff. = 4.16, 95% CI 1.52-6.81, p = 0.010). While there was no linear association between fatigue and age, a cubic relationship was identified (p < 0.001), with fatigue peaks in mid-life and the oldest old. CONCLUSION: Use of IPD meta-analysis gave us the power to identify novel factors associated with fatigue, such as longer time since stroke, as well as a non-linear relationship with age.

Outcomes among older people in a post-acute inpatient rehabilitation unit.

PURPOSE: Designated multidisciplinary rehabilitation units have been shown to provide several benefits for the frail older population. The aim of this research was to evaluate changes in strength, mobility, balance, endurance, frailty and quality of life (QoL) following a 6-week multidisciplinary inpatient rehabilitation programme. METHOD: This was a prospective, observational study performed in a post-acute multidisciplinary geriatric inpatient rehabilitation service. A consecutive sample of heterogenous frail older adults (n = 32) participated. Subjects were assessed on admission to the rehabilitation service (T1) and following 6 weeks of rehabilitation (T2). A range of outcome measures were used to assess function and QoL: Berg Balance Scale (BBS), Timed Up and Go (TUG), 6-Minute Walk Test (6MWT), Barthel Index (BI), EuroQol-Visual Analogue Scale (EQ-VAS), Clinical Frailty Scale (CFS), lower limb and grip dynamometry. RESULTS: The majority were female (n = 25), the mean age was 82.9 years (SD 6.35). The median length of stay was 49 days. Patients improved significantly between T1 and T2 assessments in the BBS (p ≤ 0.0001); TUG (p ≤ 0.0001); 6MWT (p ≤ 0.0001); BI (p ≤ 0.0001); EQ-VAS (p = 0.002); CFS (p ≤ 0.0001); and in some aspects of grip and lower limb strength. CONCLUSION: This study has demonstrated that positive outcomes occurred in a range of measures in an older, frail inpatient rehabilitation population.