Measurement of the Ratio of the Vector to Pseudoscalar Charm Semileptonic Decay Rate \Gamma(D+ > ANTI-K*0 mu+ nu)/\Gamma(D+ > ANTI-K0 mu+ nu)

Using a high statistics sample of photo-produced charm particles from the FOCUS experiment at Fermilab, we report on the measurement of the ratio of semileptonic rates \Gamma(D+ > ANTI-K pi mu+ nu)/\Gamma(D+ > ANTI-K0 mu+ nu)= 0.625 +/- 0.045 +/- 0.034. Allowing for the K pi S-wave interference measured previously by FOCUS, we extract the vector to pseudoscalar ratio \Gamma(D+ > ANTI-K*0 mu+ nu)/\Gamma(D+ > ANTI-K0 mu+ nu)= 0.594 +/- 0.043 +/- 0.033 and the ratio \Gamma(D+ > ANTI-K0 mu+ nu)/\Gamma(D+ > K- pi+ pi+)= 1.019 +/- 0.076 +/- 0.065. Our results show a lower ratio for \Gamma(D > K* \ell nu})/\Gamma(D > K \ell nu) than has been reported recently and indicate the current world average branching fractions for the decays D+ >ANTI-K0(mu+, e+) nu are low. Using the PDG world average for B(D+ > K- pi+ pi+) we extract B(D+ > ANIT-K0 mu+ nu)=(9.27 +/- 0.69 +/- 0.59 +/- 0.61)%.Comment: 15 pages, 1 figur

Healthy life-year costs of treatment speed from arrival to endovascular thrombectomy in patients with ischemic stroke: a meta-analysis of individual patient data from 7 randomized clinical trials

This meta-analysis evaluates outcomes along the full health-related quality-of-life range associated with time to endovascular thrombectomy in patients with ischemic stroke.Question What are the lifetime consequences associated with care process delays in patients with ischemic stroke who are treated with endovascular thrombectomy? Findings In this meta-analysis of pooled individual patient data from 406 adults in 7 randomized trials, delays in delivering endovascular thrombectomy were associated with marked reductions in healthy life-years after treatment. In the time interval from hospital arrival to endovascular procedure start, every 1 second of delay was associated with loss of 2.2 hours of healthy life. Meaning In this study, care delays in delivering endovascular thrombectomy to ischemic stroke patients were associated with substantial losses of healthy life-years; health care organization and workflow optimization should be a priority to facilitate faster reperfusion for acute stroke patients.Importance The benefits of endovascular thrombectomy (EVT) are time dependent. Prior studies may have underestimated the time-benefit association because time of onset is imprecisely known. Objective To assess the lifetime outcomes associated with speed of endovascular thrombectomy in patients with acute ischemic stroke due to large-vessel occlusion (LVO). Data Sources PubMed was searched for randomized clinical trials of stent retriever thrombectomy devices vs medical therapy in patients with anterior circulation LVO within 12 hours of last known well time, and for which a peer-reviewed, complete primary results article was published by August 1, 2020. Study Selection All randomized clinical trials of stent retriever thrombectomy devices vs medical therapy in patients with anterior circulation LVO within 12 hours of last known well time were included. Data Extraction/Synthesis Patient-level data regarding presenting clinical and imaging features and functional outcomes were pooled from the 7 retrieved randomized clinical trials of stent retriever thrombectomy devices (entirely or predominantly) vs medical therapy. All 7 identified trials published in a peer-reviewed journal (by August 1, 2020) contributed data. Detailed time metrics were collected including last known well-to-door (LKWTD) time; last known well/onset-to-puncture (LKWTP) time; last known well-to-reperfusion (LKWR) time; door-to-puncture (DTP) time; and door-to-reperfusion (DTR) time. Main Outcomes and Measures Change in healthy life-years measured as disability-adjusted life-years (DALYs). DALYs were calculated as the sum of years of life lost (YLL) owing to premature mortality and years of healthy life lost because of disability (YLD). Disability weights were assigned using the utility-weighted modified Rankin Scale. Age-specific life expectancies without stroke were calculated from 2017 US National Vital Statistics. Results Among the 781 EVT-treated patients, 406 (52.0%) were early-treated (LKWTP 4-12 hours). In early-treated patients, LKWTD was 188 minutes (interquartile range, 151.3-214.8 minutes) and DTP 105 minutes (interquartile range, 76-135 minutes). Among the 298 of 380 (78.4%) patients with substantial reperfusion, median DTR time was 145.0 minutes (interquartile range, 111.5-185.5 minutes). Care process delays were associated with worse clinical outcomes in LKW-to-intervention intervals in early-treated patients and in door-to-intervention intervals in early-treated and late-treated patients, and not associated with LKWTD intervals, eg, in early-treated patients, for each 10-minute delay, healthy life-years lost were DTP 1.8 months vs LKWTD 0.0 months; P < .001. Considering granular time increments, the amount of healthy life-time lost associated with each 1 second of delay was DTP 2.2 hours and DTR 2.4 hours. Conclusions and Relevance In this study, care delays were associated with loss of healthy life-years in patients with acute ischemic stroke treated with EVT, particularly in the postarrival time period. The finding that every 1 second of delay was associated with loss of 2.2 hours of healthy life may encourage continuous quality improvement in door-to-treatment times.Paroxysmal Cerebral Disorder

Public Health and Cost Benefits of Successful Reperfusion After Thrombectomy for Stroke

Background and Purpose- The benefit that endovascular thrombectomy offers to patients with stroke with large vessel occlusions depends strongly on reperfusion grade as defined by the expanded Thrombolysis in Cerebral Infarction (eTICI) scale. Our aim was to determine the lifetime health and cost consequences of the quality of reperfusion for patients, healthcare systems, and society. Methods- A Markov model estimated lifetime quality-adjusted life years (QALY) and lifetime costs of endovascular thrombectomy-treated patients with stroke based on eTICI grades. The analysis was performed over a lifetime horizon in a United States setting, adopting healthcare and societal perspectives. The reference case analysis was conducted for stroke at 65 years of age. National health and cost consequences of improved eTICI 2c/3 reperfusion rates were estimated. Input parameters were based on best available evidence. Results- Lifetime QALYs increased for every grade of improved reperfusion (median QALYs for eTICI 0/1: 2.62; eTICI 2a: 3.46; eTICI 2b: 5.42; eTICI 2c: 5.99; eTICI 3: 6.73). Achieving eTICI 3 over eTICI 2b reperfusion resulted on average in 1.31 incremental QALYs as well as healthcare and societal cost savings of $10 327 and$20 224 per patient. A 10% increase in the eTICI 2c/3 reperfusion rate of all annually endovascular thrombectomy-treated patients with stroke in the United States is estimated to yield additional 3656 QALYs and save $21.0 million and$36.8 million for the healthcare system and society, respectively. Conclusions- Improved reperfusion grants patients with stroke additional QALYs and leads to long-term cost savings. Procedural strategies to achieve complete reperfusion should be assessed for safety and feasibility, even when initial reperfusion seems to be adequate

Automatic segmentation of cerebral infarcts in follow-up computed tomography images with convolutional neural networks

Background and purpose: Infarct volume is a valuable outcome measure in treatment trials of acute ischemic stroke and is strongly associated with functional outcome. Its manual volumetric assessment is, however, too demanding to be implemented in clinical practice. Objective: To assess the value of convolutional neural networks (CNNs) in the automatic segmentation of infarct volume in follow-up CT images in a large population of patients with acute ischemic stroke. Materials and methods: We included CT images of 1026 patients from a large pooling of patients with acute ischemic stroke. A reference standard for the infarct segmentation was generated by manual delineation. We introduce three CNN models for the segmentati

Added value of multiphase CTA imaging for thrombus perviousness assessment

Purpose: Thrombus perviousness has been associated with favorable functional outcome in acute ischemic stroke (AIS) patients. Measuring thrombus perviousness on CTA may be suboptimal due to potential delay in contrast agent arrival in occluded arteries at the moment of imaging. Dynamic sequences acquired over time can potentially overcome this issue. We investigate if dynamic CTA has added value in assessing thrombus perviousness. Methods: Prospectively collected image data of AIS patients with proven occlusion of the anterior or posterior circulation with thin-slice multi-phase CTA (MCTA) and non-contrast CT were co-registered (n = 221). Thrombus attenuation increase (TAI; a perviousness measure) was measured for the arterial, venous, and delayed phase of the MCTA and time-invariant CTAs (TiCTA). Associations with favorable clinical outcome (90-day mRS ≤ 2) were assessed using univariate and multivariable regressions and calculating areas under receiver operating curves (AUC). Results: TAI determined from the arterial phase CTA was superior in the association with favorable outcome with OR = 1.21 per 10 HU increase (95%CI 1.04–1.41, AUC 0.62, p = 0.014) compared to any other phase (venous 1.14(95%CI 1.01–1.30, AUC 0.58, p = 0.033), delayed 1.046(95%CI 0.919–1.19, AUC 0.53, p = 0.50)), and TiCTA (1.15(95%CI 1.02–1.30, AUC 0.60, p = 0.022). In the multivariable model, only TAI on arterial phase was

Prediction of outcome and endovascular treatment benefit validation and update of the MR PREDICTS decision tool

BACKGROUND AND PURPOSE: Benefit of early endovascular treatment (EVT) for ischemic stroke varies considerably among patients. The MR PREDICTS decision tool, derived from MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands), predicts outcome and treatment benefit based on baseline characteristics. Our aim was to externally validate and update MR PREDICTS with data from international trials and daily clinical practice.METHODS: We used individual patient data from 6 randomized controlled trials within the HERMES (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials) collaboration to validate the original model. Then, we updated the model and performed a second validation with data from the observational MR CLEAN Registry. Primary outcome was functional independence (defined as modified Rankin Scale score 0-2) 3 months after stroke. Treatment benefit was defined as the difference between the probability of functional independence with and without EVT. Discriminative performance was evaluated using a concordance (C) statistic.RESULTS: We included 1242 patients from HERMES (633 assigned to EVT, 609 assigned to control) and 3156 patients from the MR CLEAN Registry (all of whom underwent EVT within 6.5 hours). The C-statistic for functional independence was 0.74 (95% CI, 0.72-0.77) in HERMES and, after model updating, 0.80 (0.78-0.82) in the Registry. Median predicted treatment benefit of routinely treated patients (Registry) was 10.3% (interquartile range, 5.8%-14.4%). Patients with low (<1%) predicted treatment benefit (n=135/3156 [4.3%]) had low rates of functional independence, irrespective of reperfusion status, suggesting potential absence of treatment benefit. The updated model was made available online for clinicians and researchers at .CONCLUSIONS: Because of the substantial treatment effect and small potential harm of EVT, most patients arriving within 6 hours at an endovascular-capable center should be treated regardless of their clinical characteristics. MR PREDICTS can be used to support clinical judgement when there is uncertainty about the treatment indication, when resources are limited, or before a patient is to be transferred to an endovascular-capable center.Analysis and support of clinical decision makingDevelopment and application of statistical models for medical scientific researc

Residual flow at the site of intracranial occlusion on transcranial Doppler predicts response to intravenous thrombolysis: A multi-center study

Background: We examined if transcranial Doppler (TCD) flow findings at the site of intracranial occlusions predict outcomes of stroke patients receiving intravenous rt-PA treatment. Subjects and Methods: TCD detected residual flow with the Thrombolysis in Brain Ischemia (TIBI) grading system before intravenous rt-PA bolus in patients with acute arterial intracranial occlusion. Timing and completion of early recanalization were measured for occlusive TIBI flow grades using TCD monitoring. Poor responders were defined as modified Rankin scores (mRS) &amp;gt;2 at 3 months. Results: A total of 361 patients with proximal arterial occlusion received intravenous rt-PA at 137.4 ± 36 min (median NIHSS 16). Mean age 69 ± 13, women: 168 (46.5%). Seventeen of 96 (17.7%) patients with TIBI 0, 41/124 (33.1%) with TIBI 1, 29/76 (38.2%) with TIBI 2 and 31/65 (47.7%) with TIBI 3 had achieved complete recanalization (p &amp;lt; 0.001). Higher NIHSS, SBP, glucose and lower TIBI grades were independent negative predictors of complete recanalization in the final logistic model. Patients with TIBI 0 had less probability of complete recanalization than patients with residual flow (TIBI 1-3) (ORadj 0.4, CI 95% 0.22-0.8, p = 0.008). Median time to recanalization in patients with TIBI 0 was longer (155 min, interquartile range 104-190 min) than with TIBI ≥1 (120 min, range 60-170 min, p = 0.01, Mann-Whitney U test). In the stepwise multiple linear regression models adjusting for baseline characteristics, the only 2 factors that independently associated with time to recanalization were: time to rt-PA treatment and the absent flow (TIBI 0) on baseline TCD. Absent flow (TIBI 0) was associated with a longer time of recanalization of 35.2 min (95% CI 0.3-70.1 min, p = 0.048). Poor outcomes at 3 months were found in 61.3% of patients with no residual flow (TIBI 0), 56.9% with minimal (TIBI 1), 51.5% with blunted (TIBI 2), and 33.9% with dampened (TIBI 3) flows (p = 0.012). Patients with TIBI 0 have a higher likelihood of poor outcome (OR 3.1, 95% CI 1.5-6.4, p = 0.002). Patients who achieved complete recanalization have ORadj 5.2 for good outcome (95% CI 2.8-9.8, p &amp;lt; 0.001). Conclusions: The pretreatment residual flow at intracranial occlusion predicts the likelihood of complete recanalization, time of recanalization and long-term outcome. No detectable residual flow indicates the least chance to achieve recanalization and recovery with systemic thrombolysis and may support an early decision for combined endovascular rescue. Copyright © 2008 S. Karger AG

Defining hematoma expansion in intracerebral hemorrhage: Relationship with patient outcomes

Background: Hematoma expansion (HE) is a surrogate marker in intracerebral hemorrhage (ICH) trials. However, the amount of HE necessary to produce poor outcomes in an individual is unclear; there is no agreement on a clinically meaningful definition of HE. We compared commonly used definitions of HE in their ability to predict poor outcome as defined by various cutpoints on the modified Rankin Scale (mRS). &lt;BR/&gt; &lt;BR/&gt; Methods: In this cohort study, we analyzed 531 patients with ICH from the Virtual International Stroke Trials Archive. Primary outcome was mRS at 90 days, dichotomized into 0-3 vs 4-6. Secondary outcomes included other mRS cutpoints and mRS "shift analysis." Sensitivity, specificity, and predictive values for commonly used HE definitions were calculated. &lt;BR/&gt; &lt;BR/&gt; Results: Between 13% and 32% of patients met the commonly used HE definitions. All definitions independently predicted poor outcome; positive predictive values increased with higher growth cutoffs but at the expense of lower sensitivities. All HE definitions showed higher specificity than sensitivity. Absolute growth cutoffs were more predictive than relative cutoffs when mRS 5-6 or 6 was defined as "poor outcome." &lt;BR/&gt; &lt;BR/&gt; Conclusion: HE robustly predicts poor outcome regardless of the growth definition or the outcome definition. The highest positive predictive values are obtained when using an absolute growth definition to predict more severe outcomes. Given that only a minority of patients may have clinically relevant HE, hemostatic ICH trials may need to enroll a large number of patients, or select for a population that is more likely to have HE