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首次无诱因癫痫发作后癫痫复发预后模型的外部验证及其对驾驶的影响

External validation of a prognostic model for seizure recurrence following a first unprovoked seizure and implications for driving.

作者信息

Bonnett Laura Jayne, Marson Anthony G, Johnson Anthony, Kim Lois, Sander Josemir W, Lawn Nicholas, Beghi Ettore, Leone Maurizio, Smith Catrin Tudur

机构信息

Department of Biostatistics, University of Liverpool, Liverpool, United Kingdom.

Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, United Kingdom.

出版信息

PLoS One. 2014 Jun 11;9(6):e99063. doi: 10.1371/journal.pone.0099063. eCollection 2014.

Abstract

OBJECTIVE

In the United Kingdom and other European Union countries guidelines for driving following a first unprovoked seizure require the risk of another seizure in the next year to be less than 20%. Using data from one clinical trial, we previously developed a prognostic model to inform driving guidelines. The objective of this work is to externally validate our published model and demonstrate its generalisability.

METHODS

A cohort of 620 people with a first unprovoked seizure was used to develop the original model which included variables for aetiology, first degree relative with epilepsy, seizures only while asleep, electroencephalogram, computed tomography or magnetic resonance scan result, and treatment policy. The validation cohorts consisted of 274 (United Kingdom), 305 (Italy), and 847 (Australia) people. The model was evaluated using discrimination and calibration methods. A covariate, missing from the Italian dataset, was handled via five imputation methods. Following external validation, the model was fitted to a pooled population comprising all validation datasets and the development dataset. The model was stratified by dataset.

RESULTS

The model generalised relatively well. All methods of imputation performed fairly similarly. At six months, the risk of a seizure recurrence following a first ever seizure, based on the pooled datasets, is 15% (95% CI: (12% to 18%)) for patients who are treated immediately and 18% (95% CI: (15 to 21%)) otherwise. Individuals can be reliably stratified into risk groups according to the clinical factors included in the model.

SIGNIFICANCE

Our prognostic model, used to inform driving regulations, has been validated and consequently has been proven as a valuable tool for predicting risk of seizure recurrence following a first seizure in people with various combinations of risk factors. Additionally, there is evidence to support one worldwide overall prognostic model for risk of second seizure following a first.

摘要

目的

在英国和其他欧盟国家,首次无诱因癫痫发作后的驾驶指南要求下一年再次发作的风险低于20%。我们之前利用一项临床试验的数据开发了一个预后模型,以指导驾驶指南。这项工作的目的是对我们已发表的模型进行外部验证,并证明其通用性。

方法

一组620例首次无诱因癫痫发作的患者被用于开发原始模型,该模型纳入了病因、癫痫一级亲属、仅在睡眠时发作、脑电图、计算机断层扫描或磁共振扫描结果以及治疗策略等变量。验证队列包括274例(英国)、305例(意大利)和847例(澳大利亚)患者。使用区分度和校准方法对模型进行评估。通过五种插补方法处理意大利数据集中缺失的一个协变量。在外部验证后,将模型应用于包含所有验证数据集和开发数据集的汇总人群。模型按数据集进行分层。

结果

该模型的通用性相对较好。所有插补方法的表现相当相似。基于汇总数据集,首次癫痫发作后6个月,立即接受治疗的患者癫痫复发风险为15%(95%置信区间:(12%至18%)),否则为18%(95%置信区间:(15%至21%))。根据模型中包含的临床因素,可以可靠地将个体分层到风险组。

意义

我们用于指导驾驶法规的预后模型已经得到验证,因此已被证明是预测具有各种风险因素组合的人群首次癫痫发作后癫痫复发风险的有价值工具。此外,有证据支持一个针对首次发作后第二次癫痫发作风险的全球总体预后模型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac14/4053525/79e9a03f8c00/pone.0099063.g001.jpg

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