Importance Outcome prediction after endovascular treatment (EVT) for ischemic stroke is important to patients, family members, and physicians.Objective To develop and validate a model based on... Show moreImportance Outcome prediction after endovascular treatment (EVT) for ischemic stroke is important to patients, family members, and physicians.Objective To develop and validate a model based on preprocedural and postprocedural characteristics to predict functional outcome for individual patients after EVT.Design, Setting, and Participants A prediction model was developed using individual patient data from 7 randomized clinical trials, performed between December 2010 and December 2014. The model was developed within the Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials (HERMES) collaboration and external validation in data from the Dutch Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) Registry of patients treated in clinical practice between March 2014 and November 2017. Participants included patients from multiple centers throughout different countries in Europe, North America, East Asia, and Oceania (derivation cohort), and multiple centers in the Netherlands (validation cohort). Included were adult patients with a history of ischemic stroke from an intracranial large vessel occlusion in the anterior circulation who underwent EVT within 12 hours of symptom onset or last seen well. Data were last analyzed in July 2022.Main Outcome(s) and Measure(s) A total of 19 variables were assessed by multivariable ordinal regression to predict functional outcome (modified Rankin Scale [mRS] score) 90 days after EVT. Variables were routinely available 1 day after EVT. Akaike information criterion (AIC) was used to optimize model fit vs model complexity. Probabilities for functional independence (mRS 0-2) and survival (mRS 0-5) were derived from the ordinal model. Model performance was expressed with discrimination (C statistic) and calibration.Results A total of 781 patients (median [IQR] age, 67 [57-76] years; 414 men [53%]) constituted the derivation cohort, and 3260 patients (median [IQR] age, 72 [61-80] years; 1684 men [52%]) composed the validation cohort. Nine variables were included in the model: age, baseline National Institutes of Health Stroke Scale (NIHSS) score, prestroke mRS score, history of diabetes, occlusion location, collateral score, reperfusion grade, NIHSS score at 24 hours, and symptomatic intracranial hemorrhage 24 hours after EVT. External validation in the MR CLEAN Registry showed excellent discriminative ability for functional independence (C statistic, 0.91; 95% CI, 0.90-0.92) and survival (0.89; 95% CI, 0.88-0.90). The proportion of functional independence in the MR CLEAN Registry was systematically higher than predicted by the model (41% vs 34%), whereas observed and predicted survival were similar (72% vs 75%). The model was updated and implemented for clinical use.Conclusion and relevance The prognostic tool MR PREDICTS@24H can be applied 1 day after EVT to accurately predict functional outcome for individual patients at 90 days and to provide reliable outcome expectations and personalize follow-up and rehabilitation plans. It will need further validation and updating for contemporary patients. Show less
Chesnaye, N.C.; Caskey, F.J.; Dekker, F.W.; Rooi, E.N.M. de; Evans, M.; Heimburger, O.; ... ; Kuan, Y. 2023
Background We explore longitudinal trajectories of clinical indicators, patient-reported outcomes, and hospitalizations, in the years preceding death in a population of older patients with advanced... Show moreBackground We explore longitudinal trajectories of clinical indicators, patient-reported outcomes, and hospitalizations, in the years preceding death in a population of older patients with advanced chronic kidney disease (CKD). Methods The EQUAL study is a European observational prospective cohort study with an incident eGFR Results We included 661 decedents with a median time to death of 2.0 years (IQR 0.9-3.2). During the years preceding death, eGFR, Subjective Global Assessment score, and blood pressure declined, with accelerations seen at 6 months preceding death. Serum hemoglobin, hematocrit, cholesterol, calcium, albumin, and sodium values declined slowly during follow-up, with accelerations observed between 6 and 12 months preceding death. Physical and mental quality of life declined linearly throughout follow-up. The number of reported symptoms was stable up to 2 years prior to death, with an acceleration observed at 1 year prior to death. The rate of hospitalization was stable at around one hospitalization per person year, increasing exponentially at 6 months preceding death. Conclusions We identified clinically relevant physiological accelerations in patient trajectories that began similar to 6 to 12 months prior to death, which are likely multifactorial in nature, but correlate with a surge in hospitalizations. Further research should focus on how to effectively use this knowledge to inform patient and family expectations, to benefit the planning of (end-of-life) care, and to establish clinical alert systems. Show less
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... Show moreBACKGROUND 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. Show less
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... Show moreThis 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 hours) and 375 (48.0%) were late-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. Show less
Context. Young stars with debris disks are the most promising targets for an exoplanet search because debris indicate a successful formation of planetary bodies. Debris disks can be shaped by... Show moreContext. Young stars with debris disks are the most promising targets for an exoplanet search because debris indicate a successful formation of planetary bodies. Debris disks can be shaped by planets into ring structures that give valuable indications on the presence and location of planets in the disk.Aims. We performed observations of the Sco-Cen F star HD 117214 to search for planetary companions and to characterize the debris disk structure.Methods. HD 117214 was observed with the SPHERE subsystems IRDIS, IFS, and ZIMPOL at optical and near-IR wavelengths using angular and polarimetric differential imaging techniques. This provided the first images of scattered light from the debris disk with the highest spatial resolution of 25 mas and an inner working angle <0.1 ''. With the observations with IRDIS and IFS we derived detection limits for substellar companions. The geometrical parameters of the detected disk were constrained by fitting 3D models for the scattering of an optically thin dust disk. Investigating the possible origin of the disk gap, we introduced putative planets therein and modeled the planet-disk and planet-planet dynamical interactions. The obtained planetary architectures were compared with the detection limit curves.Results. The debris disk has an axisymmetric ring structure with a radius of 0.42(0.01)'' or similar to 45 au and an inclination of 71(+/- 2.5)degrees and exhibits a 0.4 '' (similar to 40 au) wide inner cavity. From the polarimetric data, we derive a polarized flux contrast for the disk of (F-pol)(disk)/F=(3.1 +/- 1.2)x10(-4) in the RI band.Conclusions. The fractional scattered polarized flux of the disk is eight times lower than the fractional IR flux excess. This ratio is similar to the one obtained for the debris disk HIP 79977, indicating that dust radiation properties are similar for these two disks. Inside the disk cavity we achieve high-sensitivity limits on planetary companions with a mass down to similar to 4 M-J at projected radial separations between 0.2 '' and 0.4 ''. We can exclude stellar companions at a radial separation larger than 75 mas from the star. Show less
Lacy, M.; Baum, S.A.; Chandler, C.J.; Chatterjee, S.; Clarke, T.E.; Deustua, S.; ... ; Yoon, I. 2020
The chemical composition and properties of environmental media determine nanomaterial (NM) transport, fate, biouptake, and organism response. To compare and interpret experimental data, it is... Show moreThe chemical composition and properties of environmental media determine nanomaterial (NM) transport, fate, biouptake, and organism response. To compare and interpret experimental data, it is essential that sufficient context be provided for describing the physical and chemical characteristics of the setting in which a nanomaterial may be present. While the nanomaterial environmental, health and safety (NanoEHS) field has begun harmonization to allow data comparison and re-use (e.g. using standardized materials, defining a minimum set of required material characterizations), there is limited guidance for standardizing test media. Since most of the NM properties driving environmental behaviour and toxicity are medium-dependent, harmonization of media is critical. A workshop in March 2016 at Duke University identified five categories of test media: aquatic testing media, soil and sediment testing media, biological testing media, engineered systems testing media and product matrix testing media. For each category of test media, a minimum set of medium characteristics to report in all NM tests is recommended. Definitions and detail level of the recommendations for specific standardized media vary across these media categories. This reflects the variation in the maturity of their use as a test medium and associated measurement techniques, variation in utility and relevance of standardizing medium properties, ability to simplify standardizing reporting requirements, and in the availability of established standard reference media. Adoption of these media harmonization recommendations will facilitate the generation of integrated comparable datasets on NM fate and effects. This will in turn allow testing of the predictive utility of functional assay measurements on NMs in relevant media, support investigation of first principles approaches to understand behavioral mechanisms, and support categorization strategies to guide research, commercial development, and policy. Show less
Background-People with reduced glomerular filtration rate (GFR) often have elevated cardiac troponin T (cTnT) levels. It remains unclear how cTnT levels develop over time in those with chronic... Show moreBackground-People with reduced glomerular filtration rate (GFR) often have elevated cardiac troponin T (cTnT) levels. It remains unclear how cTnT levels develop over time in those with chronic kidney disease (CKD). The aim of this study was to prospectively study the association between cTnT and GFR over time in older advanced-stage CKD patients not on dialysis.Methods and Results-The EQUAL (European Quality Study) study is an observational prospective cohort study in stage 4 to 5 CKD patients aged >= 65 years not on dialysis (incident estimated GFR, <20 mL/min/1.73 m(2)). The EQUAL cohort used for the purpose of this study includes 171 patients followed in Sweden between April 2012 and December 2018. We used linear mixed models, adjusted for important groups of confounders, to investigate the effect of both measured GFR and estimated GFR on high-sensitivity cTnT (hs-cTnT) trajectory over 4 years. Almost all patients had at least 1 hs-cTnT measurement elevated above the 99th percentile of the general reference population (<= 14 ng/L). On average, hs-cTnT increased by 16%/year (95% CI, 13-19; P<0.0001). Each 15 mL/min/1.73 m(2) lower mean estimated GFR was associated with a 23% (95% CI, 14-31; P<0.0001) higher baseline hs-cTnT and 9% (95% CI, 5-13%; P<0.0001) steeper increase in hs-cTnT. The effect of estimated GFR on hs-cTnT trajectory was somewhat lower than a previous myocardial infarction (15%), but higher than presence of diabetes mellitus (4%) and male sex (5%).Conclusions-In CKD patients, hs-cTnT increases over time as renal function decreases. Lower CKD stage (each 15 mL/min/1.73 m2 lower) is independently associated with a steeper hs-cTnT increase over time in the same range as other established cardiovascular risk factors. Show less
Background Revascularization after endovascular therapy for acute ischemic stroke is measured by the Thrombolysis In Cerebral Infarction (TICI) scale, yet variability exists in scale definitions.... Show moreBackground Revascularization after endovascular therapy for acute ischemic stroke is measured by the Thrombolysis In Cerebral Infarction (TICI) scale, yet variability exists in scale definitions. We examined the degree of reperfusion with the expanded TICI (eTICI) scale and association with outcomes in the HERMES collaboration of recent endovascular trials.Methods The HERMES Imaging Core, blind to all other data, evaluated angiography after endovascular therapy in HERMES. A battery of TICI scores (mTICI, TICI, TICI2C) was used to define reperfusion of the initial target occlusion defined by non-invasive imaging and conventional angiography.Results Angiography of 801 subjects was available, including 797 defined by non-invasive imaging (154 internal carotid artery (ICA), 583 M1, 60 M2) and 748 by conventional angiography (195 ICA, 459 M1, 94 M2). Among 729 subjects in whom the reperfusion grade could be established, using eTICI (3=100%, 2C=90-99%, 2b67=67-89%, 2b50=50-66%) of the conventional angiography target occlusion, there were 63 eTICI 3 (9%), 166 eTICI 2c (23%), 218 eTICI 2b67 (30%), 103 eTICI 2b50 (14%), 100 eTICI 2a (14%), 19 eTICI 1 (3%), and 60 eTICI 0 (8%). Modified Rankin Scale shift analyses from baseline to 90 days showed that increasing TICI grades were linked with better outcomes, with significant distinctions between TICI 0/1 versus 2a (p=0.028), 2a versus 2b50 (p=0.017), and 2b50 versus 2b67 (p=0.014).Conclusions The benefit of endovascular therapy in HERMES was strongly associated with increasing degrees of reperfusion defined by eTICI. The eTICI metric identified meaningful distinctions in clinical outcomes and may be used in future studies and routine practice. Show less
