scholarly journals Impact of SAMHD1 Pharmacogenetics on Clinical Outcome in Pediatric AML

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3429-3429
Author(s):  
Richard J Marrero ◽  
Abdelrahman H Elsayed ◽  
Xueyuan Cao ◽  
Huiyun Wu ◽  
Lei Wang ◽  
...  

Abstract Acute myeloid leukemia (AML) is a heterogeneous disease characterized in part by genetic and epigenetic alterations. Cytarabine arabinoside (Ara-C) has been the cornerstone of chemotherapy treatment for patients diagnosed with AML for decades. Following cellular uptake, ara-C is phosphorylated into its active metabolite, ara-CTP, which primarily exerts its cytotoxic effects by inhibiting DNA synthesis in proliferating cells. Interpatient variation in the enzymes involved in ara-C activation/inactivation pathway (Fig 1A), can impact intracellular abundance of ara-CTP and thus its therapeutic benefit. Recently, deoxynucleoside triphosphate (dNTP) triphosphohydrolase SAM domain and HD domain 1 (SAMHD1) was shown to limit the efficacy of ara-C by intracellularly hydrolyzing its active metabolite (PMID: 27991919). Other nucleoside analogs, such as clofarabine, fludarabine, and gemcitabine have also been shown to be substrates of SAMHD1 (PMID:30305425). Among adult AML patients, higher SAMHD1 expression in the leukemic cells has been found to correlate with poor outcome (PMID: 30341277). However, whether genetic variation in SAMHD1 has any impact on the clinical outcomes in pediatric AML patients has not been evaluated in depth. In this study, we looked into 25 single nucleotide polymorphisms (SNPs) within SAMHD1 gene for their association with clinical outcome of newly diagnosed pediatric AML patients in 2 cohorts (multi-site AML02 [NCT00136084, n=167] and AML08 [NCT00703820, n=231] clinical trials). Briefly, genotypes for the 25 SNPs within SAMHD1 genes were obtained from Illumina 2.5 Omni data of AML patients. Association analysis was conducted using logistic regression models comparing minimal residual disease (MRD) positivity after treatment with chemotherapy using an unadjusted model and an adjusted model stratified by initial risk assignment of the patient determined at diagnosis (i.e. low, standard, and high). MRD positivity was defined as one or more leukemic cell per 1000 mononuclear bone-marrow cells. Cox proportional hazard models were used to examine the association of the SNPs with EFS and OS and considered three modes of inheritance. Cox regression models were performed with or without adjusting for provisional risk group assignment at time of diagnosis. Significance levels for association of SNP with clinical outcome were set at p < 0.05. Three top SNPs significantly associated with clinical outcomes were all localized in the 3'UTR region of SAMHD1(Fig 1B). Presence of the variant allele of rs7265241 was associated with a lower EFS and OS in both AML02 and AML08 cohorts. Figure 1C shows the results for OS in AML02 (HR = 2.24, 95% CI (1.05-3.55), p=0.02) and AML08 (HR = 1.52, 95% CI (1.04-1.99), p=0.01). Another 3'UTR SNP, rs1291128 was associated with poor OS in AML02 and in the clofarabine plus ara-C treatment arm in AML08 trial. For rs1291141, T allele was associated with higher MRD positivity (OR: 2.12, p=0.01) in AML02 and poor OS (HR = 1.55, 95% CI (1.12-2.14), p=0.008) in AML08(Fig 1D). Consistent with the clinical outcome results, rs1291141 T allele was also associated with higher SAMHD1 expression in the whole blood (p=8.1e-14) and several other tissues in the GTEx database. https://gtexportal.org/home/ Our results suggest that genetic variation in SAMHD1 is associated with clinical outcomes in pediatric AML patients. Future studies are aimed at looking at haplotypes and SNP-SNP combinations to establish the impact SAMHD1 pharmacogenomics on its expression within leukemic cells and subsequent response to nucleoside analogs in AML patients. SAMHD1 has also been implicated as a tumor suppressor; thus, future studies will evaluate its role both as a proliferation regulator and in drug resistance. Acknowledgements: NIH-R01-CA132946 (Lamba and Pounds), University of Florida Opportunity Seed Grant (Lamba), American Lebanese Syrian Associated Charities (ALSAC), and American Society of Hematology Bridge funding (Lamba) funded the study. We thank Drs. Campana, Coustan-Smith, and Raimondi for MRD and cytogenetic data. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Author(s):  
Jung-Won Lim ◽  
Yong-Beom Park ◽  
Dong-Hoon Lee ◽  
Han-Jun Lee

AbstractThis study aimed to evaluate whether manipulation under anesthesia (MUA) affect clinical outcome including range of motion (ROM) and patient satisfaction after total knee arthroplasty (TKA). It is hypothesized that MUA improves clinical outcomes and patient satisfaction after primary TKA. This retrospective study analyzed 97 patients who underwent staged bilateral primary TKA. MUA of knee flexion more than 120 degrees was performed a week after index surgery just before operation of the opposite site. The first knees with MUA were classified as the MUA group and the second knees without MUA as the control group. ROM, Knee Society Knee Score, Knee Society Functional Score, Western Ontario and McMaster Universities (WOMAC) score, and patient satisfaction were assessed. Postoperative flexion was significantly greater in the MUA group during 6 months follow-up (6 weeks: 111.6 vs. 99.8 degrees, p < 0.001; 3 months: 115.9 vs. 110.2 degrees, p = 0.001; 6 months: 120.2 vs. 117.0 degrees, p = 0.019). Clinical outcomes also showed similar results with knee flexion during 2 years follow-up. Patient satisfaction was significantly high in the MUA group during 12 months (3 months: 80.2 vs. 71.5, p < 0.001; 6 months: 85.8 vs. 79.8, p < 0.001; 12 months: 86.1 vs. 83.9, p < 0.001; 24 months: 86.6 vs. 85.5, p = 0.013). MUA yielded improvement of clinical outcomes including ROM, and patient satisfaction, especially in the early period after TKA. MUA in the first knee could be taken into account to obtain early recovery and to improve patient satisfaction in staged bilateral TKA.


2017 ◽  
pp. 22-24
Author(s):  
Thi Thao Nhi Tran ◽  
Dinh Toan Nguyen

Background and Purpose: Stroke is the second cause of mortality and the leading cause of disability. Using the clinical scale to predict the outcome of the patient play an important role in clinical practice. The Totaled Health Risks in Vascular Events (THRIVE) score has shown broad utility, allowing prediction of clinical outcome and death. Methods: A cross-sectional study conducting on 102 patients with acute ischemic stroke using THRIVE score. The outcome of patient was assessed by mRankin in the day of 30 after stroke. Statistic analysis using SPSS 15.0. Results: There was 60.4% patient in the group with THRIVE score 0 – 2 points having a good outcome (mRS 0 - 2), patient group with THRIVE score 6 - 9 having a high rate of bad outcome and mortality. Having a positive correlation between THRIVE score on admission and mRankin score at the day 30 after stroke with r = 0.712. THRIVE score strongly predicts clinical outcome with ROC-AUC was 0.814 (95% CI 0.735 - 0.893, p<0.001), Se 69%, Sp 84% and the cut-off was 2. THRIVE score strongly predicts mortality with ROC-AUC was 0.856 (95% CI 0.756 - 0.956, p<0.01), Se 86%, Sp 77% and the cut-off was 3. Analysis of prognostic factors by multivariate regression models showed that THRIVE score was only independent prognostic factor for the outcome of post stroke patients. Conclusions: The THRIVE score is a simple-to-use tool to predict clinical outcome, mortality in patients with ischemic stroke. Despite its simplicity, the THRIVE score performs better than several other outcome prediction tools. Key words: Ischemic stroke, THRIVE, prognosis, outcome, mortality


Author(s):  
Ga Young Yoon ◽  
Joo Hee Cha ◽  
Hak Hee Kim ◽  
Hee Jung Shin ◽  
Eun Young Chae ◽  
...  

Background: Metaplastic breast cancer (MC) is a rare disease, thus it is difficult to study its clinical outcomes. Objective: To investigate whether any clinicopathological or imaging features were associated with clinical outcome in MC. Methods: We retrospectively evaluated the clinicopathological and imaging findings, and the clinical outcomes of seventy-two pathologically confirmed MCs. We then compared these parameters between triple-negative (TNMC) and non-TNMCs (NTNMC). Results: Oval or round shape, and not-circumscribed margin were the most common findings on mammography, ultrasound (US), and magnetic resonance imaging (MRI). It was mostly a mass without calcification on mammography, and revealed complex or hypoechoic echotexture, and posterior acoustic enhancement on US, and rim enhancement, wash-out kinetics, peritumoral edema, and intratumoral necrosis on MRI. Of all 72, 64 were TNMCs, and eight were NTNMCs. Clinicopathological and imaging findings were similar between the two groups, except that MRI showed peritumoral edema more frequently in TNMCs than NTNMCs (p=0.045). There were 21 recurrences and 13 deaths. Multivariable analysis showed that larger tumor size and co-existing DCIS were significantly predictive of Disease free survival (DFS), and larger tumor size and neoadjuvant chemotherapy were significantly predictive of overall survival (OS). Conclusion: MC showed characteristic imaging findings, and some variables associated with survival outcome may help to predict prognosis.


2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Mendy M Welsink-Karssies ◽  
Sacha Ferdinandusse ◽  
Gert J Geurtsen ◽  
Carla E M Hollak ◽  
Hidde H Huidekoper ◽  
...  

Abstract Early diagnosis and dietary treatment do not prevent long-term complications, which mostly affect the central nervous system in classical galactosemia patients. The clinical outcome of patients is highly variable, and there is an urgent need for prognostic biomarkers. The aim of this study was first to increase knowledge on the natural history of classical galactosemia by studying a cohort of patients with varying geno- and phenotypes and second to study the association between clinical outcomes and two possible prognostic biomarkers. In addition, the association between abnormalities on brain MRI and clinical outcomes was investigated. Classical galactosemia patients visiting the galactosemia expertise outpatient clinic of the Amsterdam University Medical Centre were evaluated according to the International Classical Galactosemia guideline with the addition of an examination by a neurologist, serum immunoglobulin G N-glycan profiling and a brain MRI. The biomarkers of interest were galactose-1-phosphate levels and N-glycan profiles, and the clinical outcomes studied were intellectual outcome and the presence or absence of movement disorders and/or primary ovarian insufficiency. Data of 56 classical galactosemia patients are reported. The intellectual outcome ranged from 45 to 103 (mean 77 ± 14) and was &lt;85 in 62%. Movement disorders were found in 17 (47%) of the 36 tested patients. In females aged 12 years and older, primary ovarian insufficiency was diagnosed in 12 (71%) of the 17 patients. Significant differences in N-glycan peaks were found between controls and patients. However, no significant differences in either N-glycans or galactose-1-phosphate levels were found between patients with a poor (intellectual outcome &lt; 85) and normal intellectual outcome (intellectual outcome ≥ 85), and with or without movement disorders or primary ovarian insufficiency. The variant patients detected by newborn screening, with previously unknown geno- and phenotypes and currently no long-term complications, demonstrated significantly lower galactose-1-phospate levels than classical patients (P &lt; 0.0005). Qualitative analysis of the MRI’s demonstrated brain abnormalities in 18 of the 21 patients, more severely in patients with a lower intellectual outcome and/or with movement disorders. This study demonstrates a large variability in clinical outcome, which varies from a below average intelligence, movement disorders and in females primary ovarian insufficiency to a normal clinical outcome. In our cohort of classical galactosemia patients, galactose-1-phosphate levels and N-glycan variations were not associated with clinical outcomes, but galactose-1-phosphate levels did differentiate between classical and variant patients detected by newborn screening. The correlation between brain abnormalities and clinical outcome should be further investigated by quantitative analysis of the MR images. The variability in clinical outcome necessitates individual and standardized evaluation of all classical galactosemia patients.


SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A269-A269
Author(s):  
Vaishal Shah ◽  
Nancy Foldvary-Schaefer ◽  
Lu Wang ◽  
Lara Jehi ◽  
Cynthia Pena Obrea ◽  
...  

Abstract Introduction The relationship of OSA and human coronavirus (COVID-19) in the pediatric population is unknown. We postulate that OSA is associated with SARS-CoV-2 positivity and with adverse COVID-19 outcomes in children. Methods A retrospective review of 120 consecutive patients (&lt;18 years) with prior polysomnogram (PSG) and COVID-19 testing from the Cleveland Clinic COVID-19 registry was conducted. Using a case control design of SARS-CoV-2 positive and negative pediatric patients, we examined COVID-19 and pre-existing OSA (dichotomized AHI≥1) using logistic (OR,95%CI) regression and as continuous measures: AHI, oxygen(SpO2) nadir, %time SpO2&lt;90%) using linear regression(beta+/-SE). In those positive for SARS-CoV-2(cases only), we assessed the association of OSA and World Health Organization(WHO) COVID-19 clinical outcome composite score (hospitalization, requiring supplemental oxygen, non-invasive ventilation/high-flow oxygen, invasive ventilation/ECMO or death) using Wilcoxon rank sum test for ordinal data. Results Cases (n=36) were 11.8±4.4 years, 61% male, 27.8% black and 88.9% with OSA, while 85.7% of controls (n=84) had OSA. OSA was not associated with increased SARS-CoV-2 positivity: OR=1.33(0.40, 4.45,p=0.64). No significant difference between cases and controls for mean AHI 3.7(1.5,6.0) vs 3.5(1.5,7.1),p=0.91,SpO2 nadir 88.6±5.4 vs 89.1±4.4,p=0.58,%time SpO2&lt;90% 0.05[0.00,1.00) vs 0.10 (0.00,1.00, p=0.65) respectively was noted. WHO-7 COVID-19 clinical outcome did not meet statistical significance in relation to OSA due to the low event frequency (p=0.49). Of note, those with OSA vs without OSA had a higher WHO-7 outcome score of 2 vs 0 and prevalence of hospitalization: 12.5 vs 0% respectively. Of hospitalized patients, the following was observed: 23% had moderate/severe OSA vs 4.3% mild OSA, 50% required supplemental oxygen and 25% required intubation/invasive ventilation. No deaths or readmissions were reported. High risk conditions included: 75% obesity, 50% asthma, 25% sickle cell disease and 25% hypoplastic left heart. Conclusion In this first report of which we are aware focused on COVID-19 in pediatric OSA, we use a case control design leveraging COVID-19 and sleep laboratory registries. Albeit not statistically significant, pediatric patients with OSA had a higher percentage of worse clinical outcomes. Larger network studies are needed to clarify whether poorer COVID-19 outcomes may be attributable to OSA or modulated via high risk health conditions. Support (if any):


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
F Xing ◽  
X Bai ◽  
J Li

Abstract Background Whether discharge heart rate for hospitalized heart failure (HF) patients with coexisted atrial fibrillation (AF) is associated with long-term clinical outcomes and whether this association differs between patients with and without beta-blockers have not been well studied. Purpose We investigated the associations between discharge heart rate and clinical outcomes in hospitalized HF patients with coexisted AF, while stratified to beta-blockers at discharge. Methods The study cohort included 1631 HF patients hospitalized primarily with AF, which was from the China PEACE Prospective Heart Failure Study. Clinical outcome was 1-year combined all-cause mortality and HF hospitalization after discharge. We analyzed association between outcome and heart rate at discharge with restricted cubic spline and Cox proportional hazard ratios (HR). Results The median age was 68 (IQR: 60- 77) years, 41.9% were women, discharge heart rate was (median (IQR)) 75 (69- 84) beats per minute (bpm), and 60.2% received beta-blockers at discharge. According to the result of restricted cubic spline plot, the relationship between discharge heart rate and clinical outcome may be nonlinear (P&lt;0.01). Based on above result, these patients were divided into 3 groups: lowest &lt;65 bpm, middle 65–86 bpm and highest ≥87 bpm, clinical outcomes occurred in 128 (64.32%), 624 (53.42%) and 156 (59.32%) patients in the lowest, middle, and highest groups respectively. In the Cox proportional hazard analysis, the lowest and highest groups were associated with increased risks of clinical outcome compared with the middle group (HR: 1.289, 95% confidence interval (CI): 1.056 - 1.573, p=0.013; HR: 1.276, 95% CI: 1.06 - 1.537, p=0.01, respectively). And a significant interaction between discharge heart rate and beta-blocker use was observed (P&lt;0.001 for interaction). Stratified analysis showed the lowest group was associated with increased risks of clinical outcomes in patients with beta-blockers (HR: 1.584, 95% confidence interval (CI): 1.215–2.066, p=0.001). Conclusion There may be a U-curve relationship between discharge heart rate and clinical outcomes in hospitalized HF patients with coexisted AF. They may have the best clinical outcomes with heart rates of 65 - 86 bpm. And strict heart rate control (&lt;65 bpm) may be avoided for patients who discharge with beta-blockers. Figure 1 Funding Acknowledgement Type of funding source: Other. Main funding source(s): This work was supported by the National Key Research and Development Program (2017YFC1310803) from the Ministry of Science and Technology of China; the CAMS Innovation Fund for Medical Science (2017-I2M-B&R-02); the 111 Project from the Ministry of Education of China (B16005).


2021 ◽  
Vol 11 (4) ◽  
pp. 504
Author(s):  
Dalibor Sila ◽  
Markus Lenski ◽  
Maria Vojtková ◽  
Mustafa Elgharbawy ◽  
František Charvát ◽  
...  

Background: Mechanical thrombectomy is the standard therapy in patients with acute ischemic stroke (AIS). The primary aim of our study was to compare the procedural efficacy of the direct aspiration technique, using Penumbra ACETM aspiration catheter, and the stent retriever technique, with a SolitaireTM FR stent. Secondarily, we investigated treatment-dependent and treatment-independent factors that predict a good clinical outcome. Methods: We analyzed our series of mechanical thrombectomies using a SolitaireTM FR stent and a Penumbra ACETM catheter. The clinical and radiographic data of 76 patients were retrospectively reviewed. Using binary logistic regression, we looked for the predictors of a good clinical outcome. Results: In the Penumbra ACETM group we achieved significantly higher rates of complete vessel recanalization with lower device passage counts, shorter recanalization times, shorter procedure times and shorter fluoroscopy times (p < 0.001) compared to the SolitaireTM FR group. We observed no significant difference in good clinical outcomes (52.4% vs. 56.4%, p = 0.756). Predictors of a good clinical outcome were lower initial NIHSS scores, pial arterial collateralization on admission head CT angiography scan, shorter recanalization times and device passage counts. Conclusions: The aspiration technique using Penumbra ACETM catheter is comparable to the stent retriever technique with SolitaireTM FR regarding clinical outcomes.


2021 ◽  
Vol 49 (4) ◽  
pp. 982-993
Author(s):  
Anne-Sofie Agergaard ◽  
Rene B. Svensson ◽  
Nikolaj M. Malmgaard-Clausen ◽  
Christian Couppé ◽  
Mikkel H. Hjortshoej ◽  
...  

Background: Loading interventions have become a predominant treatment strategy for tendinopathy, and positive clinical outcomes and tendon tissue responses may depend on the exercise dose and load magnitude. Purpose/Hypothesis: The purpose was to investigate if the load magnitude influenced the effect of a 12-week loading intervention for patellar tendinopathy in the short term (12 weeks) and long term (52 weeks). We hypothesized that a greater load magnitude of 90% of 1 repetition maximum (RM) would yield a more positive clinical outcome, tendon structure, and tendon function compared with a lower load magnitude of 55% of 1 RM when the total exercise volume was kept equal in both groups. Study Design: Randomized clinical trial; Level of evidence, 1. Methods: A total of 44 adult participants with chronic patellar tendinopathy were included and randomized to undergo moderate slow resistance (MSR group; 55% of 1 RM) or heavy slow resistance (HSR group; 90% of 1 RM). Function and symptoms (Victorian Institute of Sport Assessment–Patella questionnaire [VISA-P]), tendon pain during activity (numeric rating scale [NRS]), and ultrasound findings (tendon vascularization and swelling) were assessed before the intervention, at 6 and 12 weeks during the intervention, and at 52 weeks from baseline. Tendon function (functional tests) and tendon structure (ultrasound and magnetic resonance imaging) were investigated before and after the intervention period. Results: The HSR and MSR interventions both yielded significant clinical improvements in the VISA-P score (mean ± SEM) (HSR: 0 weeks, 58.8 ± 4.3; 12 weeks, 70.5 ± 4.4; 52 weeks, 79.7 ± 4.6) (MSR: 0 weeks, 59.9 ± 2.5; 12 weeks, 72.5 ± 2.9; 52 weeks, 82.6 ± 2.5), NRS score for running, NRS score for squats, NRS score for preferred sport, single-leg decline squat, and patient satisfaction after 12 weeks, and these were maintained after 52 weeks. HSR loading was not superior to MSR loading for any of the measured clinical outcomes. Similarly, there were no differences in functional (strength and jumping ability) or structural (tendon thickness, power Doppler area, and cross-sectional area) improvements between the groups undergoing HSR and MSR loading. Conclusion: There was no superior effect of exercising with a high load magnitude (HSR) compared with a moderate load magnitude (MSR) for the clinical outcome, tendon structure, or tendon function in the treatment of patellar tendinopathy in the short term. Both HSR and MSR showed equally good, continued improvements in outcomes in the long term but did not reach normal values for healthy tendons. Registration: NCT03096067 (ClinicalTrials.gov identifier)


Author(s):  
Andriy Zhydkov ◽  
Mirjam Christ-Crain ◽  
Robert Thomann ◽  
Claus Hoess ◽  
Christoph Henzen ◽  
...  

AbstractThe added value of biomarkers, such as procalcitonin (PCT), C-reactive protein (CRP), and white blood cells (WBC), as adjuncts to clinical risk scores for predicting the outcome of patients with community-acquired pneumonia (CAP) is in question. We investigated the prognostic accuracy of initial and follow-up levels of inflammatory biomarkers in predicting death and adverse clinical outcomes in a large and well-defined cohort of CAP patients.We measured PCT, CRP and WBC on days 1, 3, 5, and 7 and followed the patients over 30 days. We applied multivariate regression models and area under the curve (AUC) to investigate associations between these biomarkers, the clinical risk score CURB-65, and clinical outcomes [i.e., death and intensive care unit (ICU) admission].Of 925 patients with CAP, 50 patients died and 118 patients had an adverse clinical outcome. None of the initial biomarker levels significantly improved the CURB-65 score for mortality prediction. Follow-up biomarker levels showed significant independent association with mortality at days 3, 5, and 7 and with improvements in AUC. Initial PCT and CRP levels were independent prognostic predictors of adverse clinical outcome, and levels of all biomarkers during the course of disease provided additional prognostic information.This study provides robust insights into the added prognostic value of inflammatory markers in CAP. Procalcitonin, CRP, and to a lesser degree WBC provided some prognostic information on CAP outcomes, particularly when considering their kinetics at days 5 and 7 and when looking at adverse clinical outcomes instead of mortality alone.


2016 ◽  
Vol 9 (6) ◽  
pp. 535-540 ◽  
Author(s):  
Ruchi Kabra ◽  
Timothy J Phillips ◽  
Jacqui-Lyn Saw ◽  
Constantine C Phatouros ◽  
Tejinder P Singh ◽  
...  

ObjectiveTo audit our institutional mechanical thrombectomy (MT) outcomes for acute anterior circulation stroke and examine the influence of workflow time metrics on patient outcomes.MethodsA database of 100 MT cases was maintained throughout May 2010—February 2015 as part of a statewide service provided across two tertiary hospitals (H1 and H2). Patient demographics, stroke and procedural details, blinded angiographic outcomes, and 90-day modified Rankin Scale (mRS) scores were recorded. The following time points in stroke treatment were recorded: stroke onset, hospital presentation, CT imaging, arteriotomy, and recanalization. Statistical analysis of outcomes, predictors of outcome, and differences between the hospitals was carried out.ResultsThrombolysis in Cerebral Infarction (TICI) 2b/3 reperfusion was 79%. Forty-nine per cent of patients had good clinical outcomes (mRS 0–2). In a subgroup analysis of 76 patients with premorbid mRS 0–1 and first CT performed ≤4.5 h after stroke onset, 60% had good clinical outcomes. Patient and disease characteristics were matched between the two hospitals. H1 had shorter times between hospital presentation and CT (32 vs 55 min, p=0.01), CT and arteriotomy (33 vs 69 min, p=0.00), and stroke onset and recanalization (198 vs 260 min, p=0.00). These time metrics independently predicted good clinical outcome. Median days spent at home in the first 90 days was greater at H1 (61 vs 8, p=0.04) than at H2. A greater proportion of patients treated at H1 were independent (mRS 0–2) at 90 days (54% vs 42%); however, this was not statistically significant (p=0.22).ConclusionsOutcomes similar to randomized controlled trials are attainable in ‘real-world’ settings. Workflow time metrics were independent predictors of clinical outcome, and differed between the two hospitals owing to site-specific organizational differences.


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