ABSTRACT
Objectives: Early discontinuation is common among breast cancer patients taking aromatase inhibitors (AIs). Although several predictors have been identified, it is unclear how to simultaneously consider multiple risk factors for an individual. We sought to develop a tool for prediction of AI discontinuation and to explore how predictive value of risk factors changes with time. Materials and Methods: Survival machine learning was used to predict time-to-discontinuation of AIs in 181 women who enrolled in a prospective cohort. Models were evaluated via time-dependent area under the curve (AUC), c-index, and integrated Brier score. Feature importance was analysis was conducted via Shapley Additive Explanations (SHAP) and time-dependence of their predictive value was analyzed by time-dependent AUC. Personalized survival curves were constructed for risk communication. Results: The best-performing model incorporated genetic risk factors and changes in patient-reported outcomes, achieving mean time-dependent AUC of 0.66, and AUC of 0.72 and 0.67 at 6- and 12-month cutoffs, respectively. The most significant features included variants in ESR1 and emergent symptoms. Predictive value of genetic risk factors was highest in the first year of treatment. Decrease in physical function was the strongest independent predictor at follow-up. Discussion and Conclusion: Incorporation of genomic and 3-month follow-up data improved the ability of the models to identify the individuals at risk of AI discontinuation. Genetic risk factors were particularly important for predicting early discontinuers. This study provides insight into the complex nature of AI discontinuation and highlights the importance of incorporating genetic risk factors and emergent symptoms into prediction models.
ABSTRACT
There have been over 621 million cases of COVID-19 worldwide with over 6.5 million deaths. Despite the high secondary attack rate of COVID-19 in shared households, some exposed individuals do not contract the virus. In addition, little is known about whether the occurrence of COVID-19 resistance differs among people by health characteristics as stored in the electronic health records (EHR). In this retrospective analysis, we develop a statistical model to predict COVID-19 resistance in 8,536 individuals with prior COVID-19 exposure using demographics, diagnostic codes, outpatient medication orders, and count of Elixhauser comorbidities in EHR data from the COVID-19 Precision Medicine Platform Registry. Cluster analyses identified 5 patterns of diagnostic codes that distinguished resistant from non-resistant patients in our study population. In addition, our models showed modest performance in predicting COVID-19 resistance (best performing model AUROC = 0.61). Monte Carlo simulations conducted indicated that the AUROC results are statistically significant (p < 0.001) for the testing set. We hope to validate the features found to be associated with resistance/non-resistance through more advanced association studies.
Subject(s)
COVID-19 , Humans , SARS-CoV-2 , Retrospective Studies , Machine Learning , Electronic Health RecordsABSTRACT
OBJECTIVE: The study sought to develop and apply a framework that uses a clinical phenotyping tool to assess risk for recurrent preterm birth. MATERIALS AND METHODS: We extended an existing clinical phenotyping tool and applied a 4-step framework for our retrospective cohort study. The study was based on data collected in the Genomic and Proteomic Network for Preterm Birth Research Longitudinal Cohort Study (GPN-PBR LS). A total of 52 sociodemographic, clinical and obstetric history-related risk factors were selected for the analysis. Spontaneous and indicated delivery subtypes were analyzed both individually and in combination. Chi-square analysis and Kaplan-Meier estimate were used for univariate analysis. A Cox proportional hazards model was used for multivariable analysis. RESULTS: : A total of 428 women with a history of spontaneous preterm birth qualified for our analysis. The predictors of preterm delivery used in multivariable model were maternal age, maternal race, household income, marital status, previous caesarean section, number of previous deliveries, number of previous abortions, previous birth weight, cervical insufficiency, decidual hemorrhage, and placental dysfunction. The models stratified by delivery subtype performed better than the naïve model (concordance 0.76 for the spontaneous model, 0.87 for the indicated model, and 0.72 for the naïve model). DISCUSSION: The proposed 4-step framework is effective to analyze risk factors for recurrent preterm birth in a retrospective cohort and possesses practical features for future analyses with other data sources (eg, electronic health record data). CONCLUSIONS: We developed an analytical framework that utilizes a clinical phenotyping tool and performed a survival analysis to analyze risk for recurrent preterm birth.
