scholarly journals External validation of prediction models for time to death in potential donors after circulatory death

2017 ◽  
Vol 18 (4) ◽  
pp. 890-896 ◽  
Author(s):  
A. M. M. Kotsopoulos ◽  
F. Böing-Messing ◽  
N. E. Jansen ◽  
P. Vos ◽  
W. F. Abdo
Keyword(s):  
Prediction Models ◽  
External Validation ◽  
Time To Death ◽  
Circulatory Death

scholarly journals Prediction Model for Timing of Death in Potential Donors After Circulatory Death (DCD III): Protocol for a Multicenter Prospective Observational Cohort Study (Preprint)

2019 ◽  
Author(s):  
Angela M M Kotsopoulos ◽  
Piet Vos ◽  
Nichon E Jansen ◽  
Ewald M Bronkhorst ◽  
Johannes G van der Hoeven ◽  
...  
Keyword(s):  
Cohort Study ◽  
Prediction Model ◽  
Organ Donation ◽  
Prediction Models ◽  
Circulatory Arrest ◽  
Time To Death ◽  
Family Approach ◽  
The Impact ◽  
Circulatory Death ◽  
Previous Prediction

BACKGROUND Controlled donation after circulatory death (cDCD) is a major source of organs for transplantation. A potential cDCD donor poses considerable challenges in terms of identification of those dying within the predefined time frame of warm ischemia after withdrawal of life-sustaining treatment (WLST) to circulatory arrest. Several attempts have been made to develop models predicting the time between treatment withdrawal and circulatory arrest. This time window determines whether organ donation can occur and influences the quality of the donated organs. However, the selected patients used for these models were not always restricted to potential cDCD donors (eg, patients with cancer or severe infections were also included). This severely limits the generalizability of those data. OBJECTIVE The objectives of this study are the following: (1) to develop a model predicting time to death within 60 minutes in potential cDCD patients; (2) to validate and update previous prediction models on time to death after WLST; (3) to determine timing and patient characteristics that are associated with prognostication and the decision-making process that leads to initiating end-of-life care; (4) to evaluate the impact of timing of family approach on organ donation approval; and (5) to assess the influence of variation in WLST processes on postmortem organ donor potential and actual postmortem organ donors. METHODS In this multicenter observational prospective cohort study, all patients admitted to the intensive care unit of 3 university hospitals and 3 teaching hospitals who met the criteria of the cDCD protocol as defined by the Dutch Transplant Foundation were included. The target of enrolment was set to 400 patients. Previously developed models will be refitted in our data set. To further update previous prediction models, we will apply least absolute shrinkage and selection operator (LASSO) as a tool for efficient variable selection to develop the multivariable logistic regression model. RESULTS This protocol was funded in August 2014 by the Dutch Transplant Foundation. We expect to have the results of this study in July 2020. Patient enrolment was completed in July 2018 and data collection was completed in April 2020. CONCLUSIONS This study will provide a robust multimodal prediction model, based on clinical and physiological parameters, that can predict time to circulatory arrest in cDCD donors. In addition, it will add valuable insight in the process of WLST in cDCD donors and will fill an important knowledge gap in this essential field of health care. CLINICALTRIAL ClinicalTrials.gov NCT04123275; https://clinicaltrials.gov/ct2/show/NCT04123275 INTERNATIONAL REGISTERED REPORT DERR1-10.2196/16733

scholarly journals Prediction Model for Timing of Death in Potential Donors After Circulatory Death (DCD III): Protocol for a Multicenter Prospective Observational Cohort Study

10.2196/16733 ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. e16733
Author(s):  
Angela M M Kotsopoulos ◽  
Piet Vos ◽  
Nichon E Jansen ◽  
Ewald M Bronkhorst ◽  
Johannes G van der Hoeven ◽  
...  
Keyword(s):  
Cohort Study ◽  
Prediction Model ◽  
Organ Donation ◽  
Prediction Models ◽  
Circulatory Arrest ◽  
Time To Death ◽  
Family Approach ◽  
The Impact ◽  
Circulatory Death ◽  
Previous Prediction

Background Controlled donation after circulatory death (cDCD) is a major source of organs for transplantation. A potential cDCD donor poses considerable challenges in terms of identification of those dying within the predefined time frame of warm ischemia after withdrawal of life-sustaining treatment (WLST) to circulatory arrest. Several attempts have been made to develop models predicting the time between treatment withdrawal and circulatory arrest. This time window determines whether organ donation can occur and influences the quality of the donated organs. However, the selected patients used for these models were not always restricted to potential cDCD donors (eg, patients with cancer or severe infections were also included). This severely limits the generalizability of those data. Objective The objectives of this study are the following: (1) to develop a model predicting time to death within 60 minutes in potential cDCD patients; (2) to validate and update previous prediction models on time to death after WLST; (3) to determine timing and patient characteristics that are associated with prognostication and the decision-making process that leads to initiating end-of-life care; (4) to evaluate the impact of timing of family approach on organ donation approval; and (5) to assess the influence of variation in WLST processes on postmortem organ donor potential and actual postmortem organ donors. Methods In this multicenter observational prospective cohort study, all patients admitted to the intensive care unit of 3 university hospitals and 3 teaching hospitals who met the criteria of the cDCD protocol as defined by the Dutch Transplant Foundation were included. The target of enrolment was set to 400 patients. Previously developed models will be refitted in our data set. To further update previous prediction models, we will apply least absolute shrinkage and selection operator (LASSO) as a tool for efficient variable selection to develop the multivariable logistic regression model. Results This protocol was funded in August 2014 by the Dutch Transplant Foundation. We expect to have the results of this study in July 2020. Patient enrolment was completed in July 2018 and data collection was completed in April 2020. Conclusions This study will provide a robust multimodal prediction model, based on clinical and physiological parameters, that can predict time to circulatory arrest in cDCD donors. In addition, it will add valuable insight in the process of WLST in cDCD donors and will fill an important knowledge gap in this essential field of health care. Trial Registration ClinicalTrials.gov NCT04123275; https://clinicaltrials.gov/ct2/show/NCT04123275 International Registered Report Identifier (IRRID) DERR1-10.2196/16733

scholarly journals Genetic co-expression networks contribute to creating predictive model and exploring novel biomarkers for the prognosis of breast cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Chi-Ming Chu ◽  
Huan-Ming Hsu ◽  
Chi-Wen Chang ◽  
Yuan-Kuei Li ◽  
Yu-Jia Chang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prediction Models ◽  
Reference Model ◽  
External Validation ◽  
Risk Scores ◽  
Consistent Finding ◽  
Hazard Ratios ◽  
Genetic Predictors ◽  
Novel Biomarkers ◽  
Cox Proportional Hazard Regression

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.

scholarly journals Predicting hospital admissions from individual patient data (IPD): an applied example to explore key elements driving external validity

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 ◽  
...  
Keyword(s):  
Prognostic Model ◽  
Prediction Models ◽  
Hospital Admissions ◽  
Absolute Risk ◽  
External Validation ◽  
Baseline Risk ◽  
Study Heterogeneity ◽  
Related Quality ◽  
Individual Participant ◽  
Risk Predictor

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.

scholarly journals Development and validation of prediction models for mechanical ventilation, renal replacement therapy, and readmission in COVID-19 patients

2021 ◽  
Author(s):  
Victor Alfonso Rodriguez ◽  
Shreyas Bhave ◽  
Ruijun Chen ◽  
Chao Pang ◽  
George Hripcsak ◽  
...  
Keyword(s):  
At Risk ◽  
Mechanical Ventilation ◽  
Renal Replacement Therapy ◽  
Receiver Operating Characteristic ◽  
Replacement Therapy ◽  
Operating Characteristic ◽  
Prediction Models ◽  
External Validation ◽  
Electronic Health Record Data ◽  
Receiver Operating

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.

scholarly journals Insights into the molecular properties underlying antibacterial activity of prenylated (iso)flavonoids against MRSA

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sylvia Kalli ◽  
Carla Araya-Cloutier ◽  
Jos Hageman ◽  
Jean-Paul Vincken
Keyword(s):  
Prediction Models ◽  
External Validation ◽  
Qsar Model ◽  
Prediction Errors ◽  
Activity Data ◽  
Gram Positive Bacteria ◽  
Level Of Activity ◽  
Formal Charge ◽  
Validation Set

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.

scholarly journals Models for predicting treatment efficacy of antiepileptic drugs and prognosis of treatment withdrawal in epilepsy patients

2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Shijun Yang ◽  
Bin Wang ◽  
Xiong Han
Keyword(s):  
Antiepileptic Drugs ◽  
Statistical Models ◽  
Prediction Models ◽  
External Validation ◽  
Machine Learning Algorithms ◽  
Treatment Withdrawal ◽  
Patient Treatment ◽  
Recent Developments ◽  
Progression Of Disease ◽  
Patients With Epilepsy

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.

scholarly journals Developing and validating COVID-19 adverse outcome risk prediction models from a bi-national European cohort of 5594 patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Espen Jimenez-Solem ◽  
Tonny S. Petersen ◽  
Casper Hansen ◽  
Christian Hansen ◽  
Christina Lioma ◽  
...  
Keyword(s):  
Prediction Models ◽  
Severe Disease ◽  
External Validation ◽  
Area Under The Curve ◽  
Predictive Performance ◽  
Mortality Prediction ◽  
Icu Admission ◽  
Risk Of Death ◽  
Online Risk ◽  
The United Kingdom

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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