Predicting seizure recurrence after an initial seizure-like episode from routine clinical notes using large language models: A retrospective cohort study

Background: The evaluation and management of first-time seizure-like events in children can be difficult because these episodes are not always directly observed and might be epileptic seizures or other conditions (seizure mimics). We aimed to evaluate whether machine learning models using real-world data could predict seizure recurrence after an initial seizure-like event. Methods: This retrospective cohort study compared models trained and evaluated on two separate datasets between Jan 1, 2010, and Jan 1, 2020: electronic medical records (EMRs) at Boston Children's Hospital and de-identified, patient-level, administrative claims data from the IBM MarketScan research database. The study population comprised patients with an initial diagnosis of either epilepsy or convulsions before the age of 21 years, based on International Classification of Diseases, Clinical Modification (ICD-CM) codes. We compared machine learning-based predictive modelling using structured data (logistic regression and XGBoost) with emerging techniques in natural language processing by use of large language models. Findings: The primary cohort comprised 14 021 patients at Boston Children's Hospital matching inclusion criteria with an initial seizure-like event and the comparison cohort comprised 15 062 patients within the IBM MarketScan research database. Seizure recurrence based on a composite expert-derived definition occurred in 57% of patients at Boston Children's Hospital and 63% of patients within IBM MarketScan. Large language models with additional domain-specific and location-specific pre-training on patients excluded from the study (F1-score 0·826 [95% CI 0·817-0·835], AUC 0·897 [95% CI 0·875-0·913]) performed best. All large language models, including the base model without additional pre-training (F1-score 0·739 [95% CI 0·738-0·741], AUROC 0·846 [95% CI 0·826-0·861]) outperformed models trained with structured data. With structured data only, XGBoost outperformed logistic regression and XGBoost models trained with the Boston Children's Hospital EMR (logistic regression: F1-score 0·650 [95% CI 0·643-0·657], AUC 0·694 [95% CI 0·685-0·705], XGBoost: F1-score 0·679 [0·676-0·683], AUC 0·725 [0·717-0·734]) performed similarly to models trained on the IBM MarketScan database (logistic regression: F1-score 0·596 [0·590-0·601], AUC 0·670 [0·664-0·675], XGBoost: F1-score 0·678 [0·668-0·687], AUC 0·710 [0·703-0·714]). Interpretation: Physician's clinical notes about an initial seizure-like event include substantial signals for prediction of seizure recurrence, and additional domain-specific and location-specific pre-training can significantly improve the performance of clinical large language models, even for specialised cohorts.</p

Multinational characterization of neurological phenotypes in patients hospitalized with COVID-19

Neurological complications worsen outcomes in COVID-19. To define the prevalence of neurological conditions among hospitalized patients with a positive SARS-CoV-2 reverse transcription polymerase chain reaction test in geographically diverse multinational populations during early pandemic, we used electronic health records (EHR) from 338 participating hospitals across 6 countries and 3 continents (January–September 2020) for a cross-sectional analysis. We assessed the frequency of International Classification of Disease code of neurological conditions by countries, healthcare systems, time before and after admission for COVID-19 and COVID-19 severity. Among 35,177 hospitalized patients with SARS-CoV-2 infection, there was an increase in the proportion with disorders of consciousness (5.8%, 95% confidence interval [CI] 3.7–7.8%, pFDR < 0.001) and unspecified disorders of the brain (8.1%, 5.7–10.5%, pFDR < 0.001) when compared to the pre-admission proportion. During hospitalization, the relative risk of disorders of consciousness (22%, 19–25%), cerebrovascular diseases (24%, 13–35%), nontraumatic intracranial hemorrhage (34%, 20–50%), encephalitis and/or myelitis (37%, 17–60%) and myopathy (72%, 67–77%) were higher for patients with severe COVID-19 when compared to those who never experienced severe COVID-19. Leveraging a multinational network to capture standardized EHR data, we highlighted the increased prevalence of central and peripheral neurological phenotypes in patients hospitalized with COVID-19, particularly among those with severe disease

The structural plasticity of white matter networks following anterior temporal lobe resection

Anterior temporal lobe resection is an effective treatment for refractory temporal lobe epilepsy. The structural consequences of such surgery in the white matter, and how these relate to language function after surgery remain unknown. We carried out a longitudinal study with diffusion tensor imaging in 26 left and 20 right temporal lobe epilepsy patients before and a mean of 4.5 months after anterior temporal lobe resection. The whole-brain analysis technique tract-based spatial statistics was used to compare pre- and postoperative data in the left and right temporal lobe epilepsy groups separately. We observed widespread, significant, mean 7%, decreases in fractional anisotropy in white matter networks connected to the area of resection, following both left and right temporal lobe resections. However, we also observed a widespread, mean 8%, increase in fractional anisotropy after left anterior temporal lobe resection in the ipsilateral external capsule and posterior limb of the internal capsule, and corona radiata. These findings were confirmed on analysis of the native clusters and hand drawn regions of interest. Postoperative tractography seeded from this area suggests that this cluster is part of the ventro-medial language network. The mean pre- and postoperative fractional anisotropy and parallel diffusivity in this cluster were significantly correlated with postoperative verbal fluency and naming test scores. In addition, the percentage change in parallel diffusivity in this cluster was correlated with the percentage change in verbal fluency after anterior temporal lobe resection, such that the bigger the increase in parallel diffusivity, the smaller the fall in language proficiency after surgery. We suggest that the findings of increased fractional anisotropy in this ventro-medial language network represent structural reorganization in response to the anterior temporal lobe resection, which may damage the more susceptible dorso-lateral language pathway. These findings have important implications for our understanding of brain injury and rehabilitation, and may also prove useful in the prediction and minimization of postoperative language deficits

Multinational characterization of neurological phenotypes in patients hospitalized with COVID-19

Neurological complications worsen outcomes in COVID-19. To define the prevalence of neurological conditions among hospitalized patients with a positive SARS-CoV-2 reverse transcription polymerase chain reaction test in geographically diverse multinational populations during early pandemic, we used electronic health records (EHR) from 338 participating hospitals across 6 countries and 3 continents (January-September 2020) for a cross-sectional analysis. We assessed the frequency of International Classification of Disease code of neurological conditions by countries, healthcare systems, time before and after admission for COVID-19 and COVID-19 severity. Among 35,177 hospitalized patients with SARS-CoV-2 infection, there was an increase in the proportion with disorders of consciousness (5.8%, 95% confidence interval [CI] 3.7-7.8%, pFDR < 0.001) and unspecified disorders of the brain (8.1%, 5.7-10.5%, pFDR < 0.001) when compared to the pre-admission proportion. During hospitalization, the relative risk of disorders of consciousness (22%, 19-25%), cerebrovascular diseases (24%, 13-35%), nontraumatic intracranial hemorrhage (34%, 20-50%), encephalitis and/or myelitis (37%, 17-60%) and myopathy (72%, 67-77%) were higher for patients with severe COVID-19 when compared to those who never experienced severe COVID-19. Leveraging a multinational network to capture standardized EHR data, we highlighted the increased prevalence of central and peripheral neurological phenotypes in patients hospitalized with COVID-19, particularly among those with severe disease

Denoising Autoencoders for Phenotype Stratification (DAPS) Sample Simulated Patient Data

<p>Generated with https://github.com/greenelab/DAPS/</p

Examining the Use of Real‐World Evidence in the Regulatory Process

The 21st Century Cures Act passed by the United States Congress mandates the US Food and Drug Administration to develop guidance to evaluate the use of real-world evidence (RWE) to support the regulatory process. RWE has generated important medical discoveries, especially in areas where traditional clinical trials would be unethical or infeasible. However, RWE suffers from several issues that hinder its ability to provide proof of treatment efficacy at a level comparable to randomized controlled trials. In this review article, we summarized the advantages and limitations of RWE, identified the key opportunities for RWE, and pointed the way forward to maximize the potential of RWE for regulatory purposes