External validation and comparison of two prediction models for seizure recurrence after the withdrawal of antiepileptic drugs in adult patients

Epilepsia ◽  
2019 ◽  
Vol 61 (1) ◽  
pp. 115-124 ◽  
Author(s):  
Jiahe Lin ◽  
Siqi Ding ◽  
Xueying Li ◽  
Yingjie Hua ◽  
Xinshi Wang ◽  
...  
2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Shijun Yang ◽  
Bin Wang ◽  
Xiong Han

AbstractAlthough antiepileptic drugs (AEDs) are the most effective treatment for epilepsy, 30–40% of patients with epilepsy would develop drug-refractory epilepsy. An accurate, preliminary prediction of the efficacy of AEDs has great clinical significance for patient treatment and prognosis. Some studies have developed statistical models and machine-learning algorithms (MLAs) to predict the efficacy of AEDs treatment and the progression of disease after treatment withdrawal, in order to provide assistance for making clinical decisions in the aim of precise, personalized treatment. The field of prediction models with statistical models and MLAs is attracting growing interest and is developing rapidly. What’s more, more and more studies focus on the external validation of the existing model. In this review, we will give a brief overview of recent developments in this discipline.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Chi-Ming Chu ◽  
Huan-Ming Hsu ◽  
Chi-Wen Chang ◽  
Yuan-Kuei Li ◽  
Yu-Jia Chang ◽  
...  

AbstractGenetic co-expression network (GCN) analysis augments the understanding of breast cancer (BC). We aimed to propose GCN-based modeling for BC relapse-free survival (RFS) prediction and to discover novel biomarkers. We used GCN and Cox proportional hazard regression to create various prediction models using mRNA microarray of 920 tumors and conduct external validation using independent data of 1056 tumors. GCNs of 34 identified candidate genes were plotted in various sizes. Compared to the reference model, the genetic predictors selected from bigger GCNs composed better prediction models. The prediction accuracy and AUC of 3 ~ 15-year RFS are 71.0–81.4% and 74.6–78% respectively (rfm, ACC 63.2–65.5%, AUC 61.9–74.9%). The hazard ratios of risk scores of developing relapse ranged from 1.89 ~ 3.32 (p < 10–8) over all models under the control of the node status. External validation showed the consistent finding. We found top 12 co-expressed genes are relative new or novel biomarkers that have not been explored in BC prognosis or other cancers until this decade. GCN-based modeling creates better prediction models and facilitates novel genes exploration on BC prognosis.


BMJ Open ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. e045572
Author(s):  
Andreas Daniel Meid ◽  
Ana Isabel Gonzalez-Gonzalez ◽  
Truc Sophia Dinh ◽  
Jeanet Blom ◽  
Marjan van den Akker ◽  
...  

ObjectiveTo explore factors that potentially impact external validation performance while developing and validating a prognostic model for hospital admissions (HAs) in complex older general practice patients.Study design and settingUsing individual participant data from four cluster-randomised trials conducted in the Netherlands and Germany, we used logistic regression to develop a prognostic model to predict all-cause HAs within a 6-month follow-up period. A stratified intercept was used to account for heterogeneity in baseline risk between the studies. The model was validated both internally and by using internal-external cross-validation (IECV).ResultsPrior HAs, physical components of the health-related quality of life comorbidity index, and medication-related variables were used in the final model. While achieving moderate discriminatory performance, internal bootstrap validation revealed a pronounced risk of overfitting. The results of the IECV, in which calibration was highly variable even after accounting for between-study heterogeneity, agreed with this finding. Heterogeneity was equally reflected in differing baseline risk, predictor effects and absolute risk predictions.ConclusionsPredictor effect heterogeneity and differing baseline risk can explain the limited external performance of HA prediction models. With such drivers known, model adjustments in external validation settings (eg, intercept recalibration, complete updating) can be applied more purposefully.Trial registration numberPROSPERO id: CRD42018088129.


Author(s):  
Victor Alfonso Rodriguez ◽  
Shreyas Bhave ◽  
Ruijun Chen ◽  
Chao Pang ◽  
George Hripcsak ◽  
...  

Abstract Objective Coronavirus disease 2019 (COVID-19) patients are at risk for resource-intensive outcomes including mechanical ventilation (MV), renal replacement therapy (RRT), and readmission. Accurate outcome prognostication could facilitate hospital resource allocation. We develop and validate predictive models for each outcome using retrospective electronic health record data for COVID-19 patients treated between March 2 and May 6, 2020. Materials and Methods For each outcome, we trained 3 classes of prediction models using clinical data for a cohort of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2)–positive patients (n = 2256). Cross-validation was used to select the best-performing models per the areas under the receiver-operating characteristic and precision-recall curves. Models were validated using a held-out cohort (n = 855). We measured each model’s calibration and evaluated feature importances to interpret model output. Results The predictive performance for our selected models on the held-out cohort was as follows: area under the receiver-operating characteristic curve—MV 0.743 (95% CI, 0.682-0.812), RRT 0.847 (95% CI, 0.772-0.936), readmission 0.871 (95% CI, 0.830-0.917); area under the precision-recall curve—MV 0.137 (95% CI, 0.047-0.175), RRT 0.325 (95% CI, 0.117-0.497), readmission 0.504 (95% CI, 0.388-0.604). Predictions were well calibrated, and the most important features within each model were consistent with clinical intuition. Discussion Our models produce performant, well-calibrated, and interpretable predictions for COVID-19 patients at risk for the target outcomes. They demonstrate the potential to accurately estimate outcome prognosis in resource-constrained care sites managing COVID-19 patients. Conclusions We develop and validate prognostic models targeting MV, RRT, and readmission for hospitalized COVID-19 patients which produce accurate, interpretable predictions. Additional external validation studies are needed to further verify the generalizability of our results.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sylvia Kalli ◽  
Carla Araya-Cloutier ◽  
Jos Hageman ◽  
Jean-Paul Vincken

AbstractHigh resistance towards traditional antibiotics has urged the development of new, natural therapeutics against methicillin-resistant Staphylococcus aureus (MRSA). Prenylated (iso)flavonoids, present mainly in the Fabaceae, can serve as promising candidates. Herein, the anti-MRSA properties of 23 prenylated (iso)flavonoids were assessed in-vitro. The di-prenylated (iso)flavonoids, glabrol (flavanone) and 6,8-diprenyl genistein (isoflavone), together with the mono-prenylated, 4′-O-methyl glabridin (isoflavan), were the most active anti-MRSA compounds (Minimum Inhibitory Concentrations (MIC) ≤ 10 µg/mL, 30 µM). The in-house activity data was complemented with literature data to yield an extended, curated dataset of 67 molecules for the development of robust in-silico prediction models. A QSAR model having a good fit (R2adj 0.61), low average prediction errors and a good predictive power (Q2) for the training (4% and Q2LOO 0.57, respectively) and the test set (5% and Q2test 0.75, respectively) was obtained. Furthermore, the model predicted well the activity of an external validation set (on average 5% prediction errors), as well as the level of activity (low, moderate, high) of prenylated (iso)flavonoids against other Gram-positive bacteria. For the first time, the importance of formal charge, besides hydrophobic volume and hydrogen-bonding, in the anti-MRSA activity was highlighted, thereby suggesting potentially different modes of action of the different prenylated (iso)flavonoids.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Espen Jimenez-Solem ◽  
Tonny S. Petersen ◽  
Casper Hansen ◽  
Christian Hansen ◽  
Christina Lioma ◽  
...  

AbstractPatients with severe COVID-19 have overwhelmed healthcare systems worldwide. We hypothesized that machine learning (ML) models could be used to predict risks at different stages of management and thereby provide insights into drivers and prognostic markers of disease progression and death. From a cohort of approx. 2.6 million citizens in Denmark, SARS-CoV-2 PCR tests were performed on subjects suspected for COVID-19 disease; 3944 cases had at least one positive test and were subjected to further analysis. SARS-CoV-2 positive cases from the United Kingdom Biobank was used for external validation. The ML models predicted the risk of death (Receiver Operation Characteristics—Area Under the Curve, ROC-AUC) of 0.906 at diagnosis, 0.818, at hospital admission and 0.721 at Intensive Care Unit (ICU) admission. Similar metrics were achieved for predicted risks of hospital and ICU admission and use of mechanical ventilation. Common risk factors, included age, body mass index and hypertension, although the top risk features shifted towards markers of shock and organ dysfunction in ICU patients. The external validation indicated fair predictive performance for mortality prediction, but suboptimal performance for predicting ICU admission. ML may be used to identify drivers of progression to more severe disease and for prognostication patients in patients with COVID-19. We provide access to an online risk calculator based on these findings.


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