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1. Machine learning for suicide risk prediction in children and adolescents with electronic health records

   https://doi.org/10.1038/s41398-020-01100-0  

   Su, Chang ; Aseltine, Robert ; Doshi, Riddhi ; Chen, Kun ; Rogers, Steven C. ; Wang, Fei ( December 2020 , Translational Psychiatry)

   null (Ed.)

   Abstract Accurate prediction of suicide risk among children and adolescents within an actionable time frame is an important but challenging task. Very few studies have comprehensively considered the clinical risk factors available to produce quantifiable risk scores for estimation of short- and long-term suicide risk for pediatric population. In this paper, we built machine learning models for predicting suicidal behavior among children and adolescents based on their longitudinal clinical records, and determining short- and long-term risk factors. This retrospective study used deidentified structured electronic health records (EHR) from the Connecticut Children’s Medical Center covering the period from 1 October 2011 to 30 September 2016. Clinical records of 41,721 young patients (10–18 years old) were included for analysis. Candidate predictors included demographics, diagnosis, laboratory tests, and medications. Different prediction windows ranging from 0 to 365 days were adopted. For each prediction window, candidate predictors were first screened by univariate statistical tests, and then a predictive model was built via a sequential forward feature selection procedure. We grouped the selected predictors and estimated their contributions to risk prediction at different prediction window lengths. The developed predictive models predicted suicidal behavior across all prediction windows with AUCs varying from 0.81 to 0.86. For all prediction windows, the models detected 53–62% of suicide-positive subjects with 90% specificity. The models performed better with shorter prediction windows and predictor importance varied across prediction windows, illustrating short- and long-term risks. Our findings demonstrated that routinely collected EHRs can be used to create accurate predictive models for suicide risk among children and adolescents. 

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2. Embedding electronic health records onto a knowledge network recognizes prodromal features of multiple sclerosis and predicts diagnosis

   https://doi.org/10.1093/jamia/ocab270  

   Nelson, Charlotte A ; Bove, Riley ; Butte, Atul J ; Baranzini, Sergio E ( December 2021 , Journal of the American Medical Informatics Association)

   Early identification of chronic diseases is a pillar of precision medicine as it can lead to improved outcomes, reduction of disease burden, and lower healthcare costs. Predictions of a patient’s health trajectory have been improved through the application of machine learning approaches to electronic health records (EHRs). However, these methods have traditionally relied on “black box” algorithms that can process large amounts of data but are unable to incorporate domain knowledge, thus limiting their predictive and explanatory power. Here, we present a method for incorporating domain knowledge into clinical classifications by embedding individual patient data into a biomedical knowledge graph.

   A modified version of the Page rank algorithm was implemented to embed millions of deidentified EHRs into a biomedical knowledge graph (SPOKE). This resulted in high-dimensional, knowledge-guided patient health signatures (ie, SPOKEsigs) that were subsequently used as features in a random forest environment to classify patients at risk of developing a chronic disease.

   Our model predicted disease status of 5752 subjects 3 years before being diagnosed with multiple sclerosis (MS) (AUC = 0.83). SPOKEsigs outperformed predictions using EHRs alone, and the biological drivers of the classifiers provided insight into the underpinnings of prodromal MS.

   Using data from EHR as input, SPOKEsigs describe patients at both the clinical and biological levels. We provide a clinical use case for detecting MS up to 5 years prior to their documented diagnosis in the clinic and illustrate the biological features that distinguish the prodromal MS state.

    

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3. Predicting 5‐year dementia conversion in veterans with mild cognitive impairment

   https://doi.org/10.1002/dad2.12572  

   Irwin, Chase ; Tjandra, Donna ; Hu, Chengcheng ; Aggarwal, Vinod ; Lienau, Amanda ; Giordani, Bruno ; Wiens, Jenna ; Migrino, Raymond Q. ( March 2024 , Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring)

   Identifying mild cognitive impairment (MCI) patients at risk for dementia could facilitate early interventions. Using electronic health records (EHRs), we developed a model to predict MCI to all‐cause dementia (ACD) conversion at 5 years.

   Cox proportional hazards model was used to identify predictors of ACD conversion from EHR data in veterans with MCI. Model performance (area under the receiver operating characteristic curve [AUC] and Brier score) was evaluated on a held‐out data subset.

   Of 59,782 MCI patients, 15,420 (25.8%) converted to ACD. The model had good discriminative performance (AUC 0.73 [95% confidence interval (CI) 0.72–0.74]), and calibration (Brier score 0.18 [95% CI 0.17–0.18]). Age, stroke, cerebrovascular disease, myocardial infarction, hypertension, and diabetes were risk factors, while body mass index, alcohol abuse, and sleep apnea were protective factors.

   EHR‐based prediction model had good performance in identifying 5‐year MCI to ACD conversion and has potential to assist triaging of at‐risk patients.

   Of 59,782 veterans with mild cognitive impairment (MCI), 15,420 (25.8%) converted to all‐cause dementia within 5 years.

   Electronic health record prediction models demonstrated good performance (area under the receiver operating characteristic curve 0.73; Brier 0.18).

   Age and vascular‐related morbidities were predictors of dementia conversion.

   Synthetic data was comparable to real data in modeling MCI to dementia conversion.

   An electronic health record–based model using demographic and co‐morbidity data had good performance in identifying veterans who convert from mild cognitive impairment (MCI) to all‐cause dementia (ACD) within 5 years.

   Increased age, stroke, cerebrovascular disease, myocardial infarction, hypertension, and diabetes were risk factors for 5‐year conversion from MCI to ACD.

   High body mass index, alcohol abuse, and sleep apnea were protective factors for 5‐year conversion from MCI to ACD.

   Models using synthetic data, analogs of real patient data that retain the distribution, density, and covariance between variables of real patient data but are not attributable to any specific patient, performed just as well as models using real patient data. This could have significant implications in facilitating widely distributed computing of health‐care data with minimized patient privacy concern that could accelerate scientific discoveries.

    

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4. Novel Preoperative Risk Stratification Using Digital Phenotyping Applying a Scalable Machine-Learning Approach

   https://doi.org/10.1213/ANE.0000000000006753  

   Laferrière-Langlois, Pascal ; Imrie, Fergus ; Geraldo, Marc-Andre ; Wingert, Theodora ; Lahrichi, Nadia ; van der Schaar, Mihaela ; Cannesson, Maxime ( December 2023 , Anesthesia & Analgesia)

   Classification of perioperative risk is important for patient care, resource allocation, and guiding shared decision-making. Using discriminative features from the electronic health record (EHR), machine-learning algorithms can create digital phenotypes among heterogenous populations, representing distinct patient subpopulations grouped by shared characteristics, from which we can personalize care, anticipate clinical care trajectories, and explore therapies. We hypothesized that digital phenotypes in preoperative settings are associated with postoperative adverse events including in-hospital and 30-day mortality, 30-day surgical redo, intensive care unit (ICU) admission, and hospital length of stay (LOS).

   We identified all laminectomies, colectomies, and thoracic surgeries performed over a 9-year period from a large hospital system. Seventy-seven readily extractable preoperative features were first selected from clinical consensus, including demographics, medical history, and lab results. Three surgery-specific datasets were built and split into derivation and validation cohorts using chronological occurrence. Consensusk-means clustering was performed independently on each derivation cohort, from which phenotypes’ characteristics were explored. Cluster assignments were used to train a random forest model to assign patient phenotypes in validation cohorts. We reconducted descriptive analyses on validation cohorts to confirm the similarity of patient characteristics with derivation cohorts, and quantified the association of each phenotype with postoperative adverse events by using the area under receiver operating characteristic curve (AUROC). We compared our approach to American Society of Anesthesiologists (ASA) alone and investigated a combination of our phenotypes with the ASA score.

   A total of 7251 patients met inclusion criteria, of which 2770 were held out in a validation dataset based on chronological occurrence. Using segmentation metrics and clinical consensus, 3 distinct phenotypes were created for each surgery. The main features used for segmentation included urgency of the procedure, preoperative LOS, age, and comorbidities. The most relevant characteristics varied for each of the 3 surgeries. Low-risk phenotype alpha was the most common (2039 of 2770, 74%), while high-risk phenotype gamma was the rarest (302 of 2770, 11%). Adverse outcomes progressively increased from phenotypes alpha to gamma, including 30-day mortality (0.3%, 2.1%, and 6.0%, respectively), in-hospital mortality (0.2%, 2.3%, and 7.3%), and prolonged hospital LOS (3.4%, 22.1%, and 25.8%). When combined with the ASA score, digital phenotypes achieved higher AUROC than the ASA score alone (hospital mortality: 0.91 vs 0.84; prolonged hospitalization: 0.80 vs 0.71).

   For 3 frequently performed surgeries, we identified 3 digital phenotypes. The typical profiles of each phenotype were described and could be used to anticipate adverse postoperative events.

    

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5. Assessing eligibility for lung cancer screening using parsimonious ensemble machine learning models: A development and validation study

   https://doi.org/10.1371/journal.pmed.1004287  

   Callender, Thomas ; Imrie, Fergus ; Cebere, Bogdan ; Pashayan, Nora ; Navani, Neal ; van der Schaar, Mihaela ; Janes, Sam M. ( October 2023 , PLOS Medicine)

   Risk-based screening for lung cancer is currently being considered in several countries; however, the optimal approach to determine eligibility remains unclear. Ensemble machine learning could support the development of highly parsimonious prediction models that maintain the performance of more complex models while maximising simplicity and generalisability, supporting the widespread adoption of personalised screening. In this work, we aimed to develop and validate ensemble machine learning models to determine eligibility for risk-based lung cancer screening.

   For model development, we used data from 216,714 ever-smokers recruited between 2006 and 2010 to the UK Biobank prospective cohort and 26,616 high-risk ever-smokers recruited between 2002 and 2004 to the control arm of the US National Lung Screening (NLST) randomised controlled trial. The NLST trial randomised high-risk smokers from 33 US centres with at least a 30 pack-year smoking history and fewer than 15 quit-years to annual CT or chest radiography screening for lung cancer. We externally validated our models among 49,593 participants in the chest radiography arm and all 80,659 ever-smoking participants in the US Prostate, Lung, Colorectal and Ovarian (PLCO) Screening Trial. The PLCO trial, recruiting from 1993 to 2001, analysed the impact of chest radiography or no chest radiography for lung cancer screening. We primarily validated in the PLCO chest radiography arm such that we could benchmark against comparator models developed within the PLCO control arm. Models were developed to predict the risk of 2 outcomes within 5 years from baseline: diagnosis of lung cancer and death from lung cancer. We assessed model discrimination (area under the receiver operating curve, AUC), calibration (calibration curves and expected/observed ratio), overall performance (Brier scores), and net benefit with decision curve analysis.

   Models predicting lung cancer death (UCL-D) and incidence (UCL-I) using 3 variables—age, smoking duration, and pack-years—achieved or exceeded parity in discrimination, overall performance, and net benefit with comparators currently in use, despite requiring only one-quarter of the predictors. In external validation in the PLCO trial, UCL-D had an AUC of 0.803 (95% CI: 0.783, 0.824) and was well calibrated with an expected/observed (E/O) ratio of 1.05 (95% CI: 0.95, 1.19). UCL-I had an AUC of 0.787 (95% CI: 0.771, 0.802), an E/O ratio of 1.0 (95% CI: 0.92, 1.07). The sensitivity of UCL-D was 85.5% and UCL-I was 83.9%, at 5-year risk thresholds of 0.68% and 1.17%, respectively, 7.9% and 6.2% higher than the USPSTF-2021 criteria at the same specificity. The main limitation of this study is that the models have not been validated outside of UK and US cohorts.

   We present parsimonious ensemble machine learning models to predict the risk of lung cancer in ever-smokers, demonstrating a novel approach that could simplify the implementation of risk-based lung cancer screening in multiple settings.

    

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