External Validation of START nomogram to predict 3-Month unfavorable outcome in Chinese acute stroke patients

https://doi.org/10.1016/j.jstrokecerebrovasdis.2019.02.032Get rights and content

Abstract

Background

Recently, the NIHSS STroke Scale score, Age, pre-stroke mRS score, onset-to-treatment Time (START nomogram) predicts 3-month functional outcome after intravenous thrombolysis in ischemic stroke patients. However, this model has not yet been an external validation. We aim to validate the performance of START nomogram.

Methods

Data were derived from the stroke center of the Nanjing First Hospital (China). Patients who lacked the necessary data to calculate the nomogram and missed 3-month modified Ranking scale scores were excluded. Modified Rankin Scale score more than 2 at 3-month was assessed as an unfavorable outcome. We used areas under the receiver operator characteristic curves (AUC-ROC) to quantify the prognostic value. Calibration was assessed by calibration plots and Hosmer-Lemeshow (HL) goodness of fit test.

Result

The final cohort included 306 eligible patients. For 3-month unfavorable outcome, the AUC-ROC of the START nomogram was .766 (95%CI: .7013-.8304, P < .0001), suggesting good discrimination in the START nomogram. It also showed good calibration (HL goodness of fit test P = .1261) in the external validation sample.

Conclusion

The START nomogram with good predictive performance is a reliable and simple clinical instrument to predict unfavorable outcome after acute stroke.

Introduction

Stroke is the second leading global cause of death behind ischemic heart disease.1 Among them, acute ischemic stroke (AIS) is the most common type of stroke.2 The treatment of choice for most patients with AIS is intravenous thrombolysis (IVT) with recombinant tissue plasminogen activator (Alteplase).3

For making decisions in patient care management, most clinical physicians use their clinical experience to predict outcomes of patients. The accuracy of these informal predictions is unclear.4 Prognostic models are good tools that may inform patients with a certain condition about their future outcome or help to judge subsequent treatment possibilities.5 Several prognostic models had been developed to predict outcome after IVT for AIS.6, 7, 8, 9, 10, 11 Only 2 developed scores were designed to predict 3-month unfavorable functional outcome after IVT for AIS, such as (hyper) Dense cerebral artery sign/early infarct signs on admission CT scan, prestroke modified Rankin Scale (mRS) score, Age, Glucose level at baseline, Onset-to-treatment time, and baseline National Institutes of Health Stroke Scale score (DRAGON score)8 and Age (A), severity of stroke (S) measured by admission NIH Stroke Scale score, stroke onset to admission time (T), range of visual fields (R), acute glucose (A), and level of consciousness (L) (ASTRAL score),9 which had been validated externally by European12, 13 and Chinese population.14 However, these scores for individualized prediction of outcome after IVT are limited by the use of dichotomization/categorization of continuous variables such as NIHSS score and age, for the disadvantage of dichotomization is that it does not make use of within-category information and lead to the loss of information.5

Recently, NIHSS STroke Scale score, Age, pre-stroke mRS score, onset-to-treatment Time (START) nomogram, the first nomogram developed by using a continuous score and including 4 strongest continuous predictors in IVT stroke patients, was validated internally in multicenter Italy cohorts,15 which reliably calculates the probability of unfavorable outcome. Nomogram is actually a visualization of a complex mathematical formula that uses traditional statistical methods such as multivariable logistic regression or Cox proportional hazards analysis to calculate the continuous probability of event of interest which is entirely based on the individual's disease characteristics, without averaging or combining within a category.16, 17 Nomogram which considers patients’ clinical characteristics is widely used to predict outcome of patients in cancer, surgery, and other specialties to make important treatment decisions.18, 19, 20, 21, 22, 23 Compared with previous risk scores, the nomograms were more accurate and have better performance characteristics.16, 24, 25 Moreover, the START nomogram did not require the interpretation of imaging or other precise measures to predict the functional outcome. Therefore, for busy clinicians, the START nomogram was simpler and easier to predict functional outcome in routine practice.

However, there has not yet been an external validation specifically in START nomogram whether in the European or Chinese population, therefore its application and promotion are limited. Especially in the Chinese population. This is the first paper to validate START nomogram externally. The purpose of this study is to evaluate the performance of START nomogram in Chinese AIS patients receiving IVT.

Section snippets

Study Participants and Data Collection

Patients included in this study were from the database of the stroke center (SC) of the Nanjing First Hospital (China). The scientific use of the data obtained from the Nanjing First Hospital Stroke Registry was approved by the Ethics Committees of Nanjing First Hospital, in accord with the Helsinki declaration in accordance to the internal protocol. Patients receiving IVT for AIS were collected. Modified Rankin Scale (mRS) more than 2 at 3-month was defined as unfavorable outcome. The

Result

A total of 3419 patients registered in the Nanjing First Hospital Stroke Registry cohort, baseline characteristics of the selected 306 patients are shown in Table 1. Among the 306 eligible patients, 97 patients had unfavorable outcome, 32% patients were female, and the mean age of the patients were 68.2 ± 12.3 years. The mean NIHSS score on admission was 7.9 ± 5.7. Among them, history of hypertension, diabetes mellitus, coronary artery disease, atrial fibrillation, and previous stroke were

Discussion

The present study externally validated the START nomogram in Chinese AIS patients. It suggested that the START nomogram displayed good discrimination and calibration. This study is the first external validation of START nomogram.

To the best of our knowledge, the START model was recently first prognostic model by using nomogram for individualized prediction of probability of 3-month unfavorable outcome after IVT for stroke patients. Comparing to other clinical prediction tools (risk groupings,

Conflicting Interests

The authors declare that there is no conflict of interest.

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  • Funding Sources Statement: This study was supported by National Natural Science Foundation of China grant 81673511, Jiangsu key Research and Development Plan grant BE2017613, Jiangsu Six Talent Peaks Project grant WSN-151, and Nanjing Medical Science and Technique Development Foundation grant QRX17020 and ZKX15027.

    1

    BaiLi Song and XiangLiang Chen contributed equally to this work.

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