Cardiac Comorbidity Risk Score: Zero-Burden Machine Learning to Improve Prediction of Postoperative Major Adverse Cardiac Events in Hip and Knee Arthroplasty.

Background In this retrospective, observational study we introduce the Cardiac Comorbidity Risk Score, predicting perioperative major adverse cardiac events (MACE) after elective hip and knee arthroplasty. MACE is a rare but important driver of mortality, and existing tools, eg, the Revised Cardiac Risk Index demonstrate only modest accuracy. We demonstrate an artificial intelligence-based approach to identify patients at high risk of MACE within 4 weeks (primary outcome) of arthroplasty, that imposes zero additional burden of cost/resources. Methods and Results Cardiac Comorbidity Risk Score calculation uses novel machine learning to estimate MACE risk from patient electronic health records, without requiring blood work or access to any demographic data beyond that of sex and age, and accounts for variable/missing/incomplete information across patient records. Validated on a deidentified cohort (age >45 years, n=445 391), performance was evaluated using the area under the receiver operator characteristics curve (AUROC), sensitivity/specificity, positive predictive value, and positive/negative likelihood ratios. In our cohort (age 63.5±10.5 years, 58.2% women, 34.2%/65.8% hip/knee procedures), 0.19% (882) experienced the primary outcome. Cardiac Comorbidity Risk Score achieved area under the receiver operator characteristics curve=80.0±0.4% (95% CI) for women and 80.1±0.5% (95% CI) for males, with 36.4% and 35.1% sensitivities, respectively, at 95% specificity, significantly outperforming Revised Cardiac Risk Index across all studied age-, sex-, risk-, and comorbidity-based subgroups. Conclusions Cardiac Comorbidity Risk Score, a novel artificial intelligence-based screening tool using known and unknown comorbidity patterns, outperforms state-of-the-art in predicting MACE within 4 weeks postarthroplasty, and can identify patients at high risk that do not demonstrate traditional risk factors.

Screening for idiopathic pulmonary fibrosis using comorbidity signatures in electronic health records.

Idiopathic pulmonary fibrosis (IPF) is a lethal fibrosing interstitial lung disease with a mean survival time of less than 5 years. Nonspecific presentation, a lack of effective early screening tools, unclear pathobiology of early-stage IPF and the need for invasive and expensive procedures for diagnostic confirmation hinder early diagnosis. In this study, we introduce a new screening tool for IPF in primary care settings that requires no new laboratory tests and does not require recognition of early symptoms. Using subtle comorbidity signatures identified from the history of medical encounters of individuals, we developed an algorithm, called the zero-burden comorbidity risk score for IPF (ZCoR-IPF), to predict the future risk of an IPF diagnosis. ZCoR-IPF was trained on a national insurance claims database and validated on three independent databases, comprising a total of 2,983,215 participants, with 54,247 positive cases. The algorithm achieved positive likelihood ratios greater than 30 at a specificity of 0.99 across different cohorts, for both sexes, and for participants with different risk states and history of confounding diseases. The area under the receiver-operating characteristic curve for ZCoR-IPF in predicting IPF exceeded 0.88 and was approximately 0.84 at 1 and 4 years before a conventional diagnosis, respectively. Thus, if adopted, ZCoR-IPF can potentially enable earlier diagnosis of IPF and improve outcomes of disease-modifying therapies and other interventions.

Reduced false positives in autism screening via digital biomarkers inferred from deep comorbidity patterns.

Here, we develop digital biomarkers for autism spectrum disorder (ASD), computed from patterns of past medical encounters, identifying children at high risk with an area under the receiver operating characteristic exceeding 80% from shortly after 2 years of age for either sex, and across two independent patient databases. We leverage uncharted ASD comorbidities, with no requirement of additional blood work, or procedures, to estimate the autism comorbid risk score (ACoR), during the earliest years when interventions are the most effective. ACoR has superior predictive performance to common questionnaire-based screenings and can reduce their current socioeconomic, ethnic, and demographic biases. In addition, we can condition on current screening scores to either halve the state-of-the-art false-positive rate or boost sensitivity to over 60%, while maintaining specificity above 95%. Thus, ACoR can significantly reduce the median diagnostic age, reducing diagnostic delays and accelerating access to evidence-based interventions.