Distinguishing between stroke subtypes and knowing the time of stroke onset are critical in clinical practice. Thrombolysis and thrombectomy are very effective treatments in selected patients with ...acute ischemic stroke. Neuroimaging helps decide who should be treated and how they should be treated but is expensive, not always available and can have contraindications. These limitations contribute to the under use of these reperfusion therapies.
An alternative approach in acute stroke diagnosis is to identify blood biomarkers which reflect the body's response to the damage caused by the different types of stroke. Specific blood biomarkers capable of differentiating ischemic from hemorrhagic stroke and mimics, identifying large vessel occlusion and capable of predicting stroke onset time would expedite diagnosis and increase eligibility for reperfusion therapies.
To date, measurements of candidate biomarkers have usually occurred beyond the time window for thrombolysis. Nevertheless, some candidate markers of brain tissue damage, particularly the highly abundant glial structural proteins like GFAP and S100β and the matrix protein MMP-9 offer promising results. Grouping of biomarkers in panels can offer additional specificity and sensitivity for ischemic stroke diagnosis. Unbiased "omics" approaches have great potential for biomarker identification because of greater gene, protein, and metabolite coverage but seem unlikely to be the detection methodology of choice because of their inherent cost.
To date, despite the evolution of the techniques used in their evaluation, no individual candidate or multimarker panel has proven to have adequate performance for use in an acute clinical setting where decisions about an individual patient are being made. Timing of biomarker measurement, particularly early when decision making is most important, requires urgent and systematic study.
BACKGROUND AND PURPOSE—Clinical large vessel occlusion (LVO) triage scales were developed to identify and bypass LVO to endovascular centers. However, there are concerns that scale misclassification ...of patients may cause excessive harm. We studied the settings where misclassifications were likely to occur and the consequences of these misclassifications in a representative stroke population.
METHODS—Prospective data were collected from consecutive ambulance-initiated stroke alerts at 2 stroke centers, with patients stratified into typical (LVO with predefined severe syndrome and non-LVO without) or atypical presentations (opposite situations). Five scales (Rapid Arterial Occlusion Evaluation RACE, Los Angeles Motor Scale LAMS, Field Assessment Stroke Triage for Emergency Destination FAST-ED, Prehospital Acute Stroke Severity scale PASS, and Cincinnati Prehospital Stroke Severity Scale CPSSS) were derived from the baseline National Institutes of Health Stroke Scale scored by doctors and analyzed for diagnostic performance compared with imaging.
RESULTS—Of a total of 565 patients, atypical presentations occurred in 31 LVO (38% of LVO) and 50 non-LVO cases (10%). Most scales correctly identified >95% of typical presentations but <20% of atypical presentations. Misclassification attributable to atypical presentations would have resulted in 4 M1/internal carotid artery occlusions, with National Institutes of Health Stroke Scale score ≥6 (5% of LVO) being missed and 9 non-LVO infarcts (5%) bypassing the nearest thrombolysis center.
CONCLUSIONS—Atypical presentations accounted for the bulk of scale misclassifications, but the majority of these misclassifications were not detrimental, and use of LVO scales would significantly increase timely delivery to endovascular centers, with only a small proportion of non-LVO infarcts bypassing the nearest thrombolysis center. Our findings, however, would require paramedics to score as accurately as doctors, and this translation is made difficult by weaknesses in current scales that need to be addressed before widespread adoption.
Factors contributing to cerebral edema in the post-hyperacute period of ischemic stroke (first 24-72 hours) are poorly understood. Blood-brain barrier (BBB) disruption and postischemic hyperperfusion ...reflect microvascular dysfunction and are associated with hemorrhagic transformation. We investigated the relationships between BBB integrity, cerebral blood flow, and space-occupying cerebral edema in patients who received acute reperfusion therapy.
We performed a pooled analysis of patients treated for anterior circulation large vessel occlusion in the EXTEND-IA TNK and EXTEND-IA TNK part 2 trials who had MRI with dynamic susceptibility contrast-enhanced perfusion-weighted imaging 24 hours after treatment. We investigated the associations between BBB disruption and cerebral blood flow within the infarct with cerebral edema assessed using 2 metrics: first midline shift (MLS) trichotomized as an ordinal scale of negligible (<1 mm), mild (≥1 to <5 mm), or severe (≥5 mm), and second relative hemispheric volume (rHV), defined as the ratio of the 3-dimensional volume of the ischemic hemisphere relative to the contralateral hemisphere.
Of 238 patients analyzed, 133 (55.9%) had negligible, 93 (39.1%) mild, and 12 (5.0%) severe MLS at 24 hours. The associated median rHV was 1.01 (IQR, 1.00-1.028), 1.03 (IQR, 1.01-1.077), and 1.15 (IQR, 1.08-1.22), respectively. MLS and rHV were associated with poor functional outcome at 90 days (
.002). Increased BBB permeability was independently associated with more edema after adjusting for age, occlusion location, reperfusion, parenchymal hematoma, and thrombolytic agent used (MLS cOR, 1.12 95% CI, 1.03-1.20,
=0.005; rHV β, 0.39 95% CI, 0.24-0.55,
<0.0001), as was reduced cerebral blood flow (MLS cOR, 0.25 95% CI, 0.10-0.58,
=0.001; rHV β, -2.95 95% CI, -4.61 to -11.29,
=0.0006). In subgroup analysis of patients with successful reperfusion (extended Treatment in Cerebral Ischemia 2b-3, n=200), reduced cerebral blood flow remained significantly associated with edema (MLS cOR, 0.37 95% CI, 0.14-0.98,
=0.045; rHV β, -2.59 95% CI, -4.32 to -0.86,
=0.004).
BBB disruption and persistent hypoperfusion in the infarct after reperfusion treatment is associated with space-occupying cerebral edema. Further studies evaluating microvascular dysfunction during the post-hyperacute period as biomarkers of poststroke edema and potential therapeutic targets are warranted.
To estimate the short term (5 years) and long term (30 years) economic burden of stroke among younger adults (18-64 years), and to calculate the loss of health-related quality of life in these ...individuals, in Australia.
A Markov microsimulation model was built to simulate incidence of stroke among younger adults in Australia. Younger adults with stroke commenced in the model via health states defined by the modified Rankin Scale at 12 months from the AVERT study (A Very Early Rehabilitation Trial), and transitioned through these health states. Costs in Australian dollars (AUD) were measured from a societal perspective for a 2018 reference year and categorised into medical, non-medical and indirect costs. Probabilistic sensitivity analyses were performed to test the robustness around the cost of illness estimates. The loss of health-related quality of life due to stroke among younger adults was calculated by determining the difference in estimated quality-adjusted life years (QALYs) between the stroke population and the general population. This was determined by multiplying the predicted remaining life years for the modelled stroke cohort and the age-matched general population, by their corresponding age-dependent utilities.
The economic burden of stroke among younger adults was estimated to be AUD2.0 billion over 5 years, corresponding to a mean of $149,180 per stroke patient. Over 30 years, the economic impact was AUD3.4 billion, equating to a mean of $249,780 per case. Probabilistic sensitivity analyses revealed a mean cost per patient of $153,410 in the short term, and a mean cost per patient of $273,496 in the long term. Compared to the age-matched general population, younger adults with stroke experienced a loss of 4.58 life years and 9.21 QALYs.
The results of our study suggests high economic and health burden of stroke among younger adults and highlights the need for preventive interventions targeting this age group.
ACTRN12606000185561 , retrospectively registered.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
regaining functional independence is an important goal for people who have experienced stroke. We hypothesized that introducing earlier and more intensive out-of-bed activity after stroke would ...reduce time to unassisted walking and improve independence in activities of daily living.
a Very Early Rehabilitation Trial (AVERT) was a phase II randomized controlled trial. Patients with confirmed stroke (infarct or hemorrhage) admitted <24 hours after stroke and who met physiological safety criteria were eligible. Patients randomized to the very early and intensive mobilization group were mobilized within 24 hours of stroke and at regular intervals thereafter. Control patients received standard stroke unit care. The primary outcome for this analysis was the number of days required to return to walking 50 m unassisted. Secondary outcomes were the Barthel Index and Rivermead Motor Assessment at 3 and 12 months after stroke.
seventy-one stroke patients with a mean age of 74.7 years were recruited from 2 hospitals. Adjusted Cox regression indicated that very early and intensive mobilization group patients returned to walking significantly faster than did standard stroke unit care controls (P=0.032; median 3.5 vs 7.0 days). Multivariable regression revealed that exposure to very early and intensive mobilization was independently associated with good functional outcome on the Barthel Index at 3 months (P=0.008) and on the Rivermead Motor Assessment at 3 (P=0.050) and 12 (P=0.024) months.
earlier and more intensive mobilization after stroke may fast-track return to unassisted walking and improve functional recovery. Clinical Trial Registration- This trial was not registered because enrollment began before July 2005.
BACKGROUND AND PURPOSE—Interhospital transfer is a critical component in the treatment of acute anterior circulation large vessel occlusive stroke transferred for mechanical thrombectomy. Real-world ...data for benchmarking and theoretical modeling are limited. We sought to characterize transfer workflow from primary stroke center (PSC) to comprehensive stroke center after the publication of positive thrombectomy trials.
METHODS—Consecutive patients transferred from 3 high-volume PSCs to a single comprehensive stroke center between January 2015 and August 2016 were included in a retrospective study. Factors associated with key time metrics were analyzed with emphasis on PSC intrahospital workflow.
RESULTS—Sixty-seven patients were identified. Median age was 74 years (interquartile range IQR, 63.5–78) and National Institutes of Health Stroke Scale 17 (IQR, 12–21). Median transfer time measured by PSC-door-to-comprehensive stroke center-door was 128 minutes (IQR, 107–164), of which 82.8% was spent at PSCs (door-in-door-out DIDO; 106 minutes; IQR, 86–143). The lengthiest component of DIDO was computed-tomography-to-retrieval-request (median 59.5 minutes; IQR, 44–83). The 37.3% had DIDO exceeding 120 minutes. DIDO times differed significantly between PSCs (P=0.01). In multivariate analyses, rerecruiting the initial ambulance crew for transfer (P<0.01) and presentation during working hours (P=0.04) were associated with shorter DIDO times.
CONCLUSIONS—In a metropolitan hub-and-spoke network, PSC-door-to-comprehensive stroke center-door and DIDO times are long even in high-volume PSCs. Improving PSC workflow represents a major opportunity to expedite mechanical thrombectomy and improve patient outcomes.
Stroke is the third most common cause of death and the sixth most common cause of disability worldwide. Treating acute ischemic stroke with thrombolytic therapy within 4.5hours from symptom onset is ...effective in improving patient outcomes. The time from stroke onset to arrival to hospital has been identified as the single most important issue in determining patients' eligibility for stroke thrombolysis. There is a need for simultaneous systemic evaluation of multi-factorial interventions in pre-hospital acute care systems, aimed at increasing patients' eligibility for stroke thrombolysis. In this paper an OR solution is proposed in the form of a simulation model that provides clear measure of the relative benefit of alternative potential interventions, demonstrating how OR modeling can be used for providing decision support in pre-hospital stroke care operations and contributing to health OR literature.
Stroke is costly, although little is known about the long-term costs of survivors of stroke. In previous cost-of-illness studies, lifetime costs have been modeled based on estimates to 5 years after ...stroke. Building on previous work from the North East Melbourne Stroke Incidence Study (NEMESIS), we aimed to describe resource use at 10 years and recalculate the lifetime societal costs of ischemic and hemorrhagic (intracerebral hemorrhage) stroke.
Ten-year patient-level resource use data were obtained and updated prices and population demographic statistics for 2010 were applied to our cost-of-illness models. We incorporated incidence data from a larger study region of NEMESIS than that used in the previous model and new 10-year survival and recurrent stroke rates. One-way sensitivity and probabilistic multivariable uncertainty analyses were undertaken.
For ischemic stroke, the overall average annual direct costs at 10 years (US dollars USD 5207) were comparable to those for survivors between 3 and 5 years (USD5438). However, the contribution of some costs varied (eg, medications contributed 13% at 5 years and 20% at 10 years). For intracerebral hemorrhage, annual direct costs were considerably (24%) greater at 10 years than estimated using 3 to 5 year data. Greater average lifetime costs per case were found using the updated models (ischemic stroke: previous model USD51806 and current USD68 769; intracerebral hemorrhage: previous model USD43 786 and current USD54 956 per case). Following sensitivity and multivariable uncertainty analyses, the findings were robust.
Costs to 10 years after stroke have not previously been reported. Our findings demonstrate the importance of estimating resource use over longer periods for forecasting lifetime estimates.
Around 15 years have now elapsed since thrombolysis was first shown to be effective for treating acute ischemic stroke, but therapeutic uptake has been modest. As outlined in this Review, research ...efforts are being directed towards rectifying this situation in a number of ways. First, strategies to enhance thrombolytic efficacy are being tested; these include intravenous and intra-arterial bridging protocols, sonothrombolysis, and the use of alternative thrombolytic agents. Second, means of extending the 4.5-h therapeutic time window up to 6 h, or even up to 9 h in patients selected on the basis of imaging, are being investigated in clinical trials. Prolongation of the time window using neuroprotection to 'freeze' penumbral tissue is also being attempted. Third, attempts are underway to reduce the risk of symptomatic intracerebral hemorrhage (currently affecting about 7% of cases) by refining imaging selection criteria, and through the use of alternative thrombolytic agents, lower doses of tissue plasminogen activator, blood-based biomarkers, and neuroprotectants. Last, in an effort to include more people within the currently accepted therapeutic time window, improvements in prehospital management strategies are being introduced. Elimination of prehospital and in-hospital delays is an urgent priority.
People suffering different types of stroke have differing demographic characteristics and survival. However, current estimates of disease burden are based on the same underlying assumptions ...irrespective of stroke type. We hypothesized that average Quality Adjusted Life Years (QALYs) lost from stroke would be different for ischemic stroke and intracerebral hemorrhage (ICH).
We used 1 and 5-year data collected from patients with first-ever stroke participating in the North East Melbourne Stroke Incidence Study (NEMESIS). We calculated case fatality rates, health-adjusted life expectancy, and quality-of-life (QoL) weights specific to each age and gender category. Lifetime 'health loss' for first-ever ischemic stroke and ICH surviving 28-days for the 2004 Australian population cohort was then estimated. Multivariable uncertainty analyses and sensitivity analyses (SA) were used to assess the impact of varying input parameters e.g. case fatality and QoL weights.
Paired QoL data at 1 and 5 years were available for 237 NEMESIS participants. Extrapolating NEMESIS rates, 31,539 first-ever strokes were expected for Australia in 2004. Average discounted (3%) QALYs lost per first-ever stroke were estimated to be 5.09 (SD 0.20; SA 5.49) for ischemic stroke (n = 27,660) and 6.17 (SD 0.26; SA 6.45) for ICH (n = 4,291; p < 0.001). QALYs lost also differed according to gender for both subtypes (ischemic stroke: males 4.69 SD 0.38, females 5.51 SD 0.46; ICH: males 5.82 SD 0.67, females 6.50 SD 0.40).
People with ICH incurred greater loss of health over a lifetime than people with ischemic stroke. This is explained by greater stroke related case fatality at a younger age, but longer life expectancy with disability after the first 12 months for people with ICH. Thus, studies of disease burden in stroke should account for these differences between subtype and gender. Otherwise, in countries where ICH is more common, health loss for stroke may be underestimated. Similar to other studies of this type, the generalisability of the results may be limited. Sensitivity and uncertainty analyses were used to provide a plausible range of variation for Australia. In countries with demographic and life expectancy characteristics comparable to Australia, our QoL weights may be reasonably applicable.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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