Rare diseases are a collection of unusual pathologies that afflict millions of individuals globally. However, the creation of treatments for these conditions is frequently limited due to the high expenses and lack of profitability associated with drug development. Orphan drugs, which are medications specifically designed for rare diseases, have played a pivotal role in treating these diseases over the past several years. Nevertheless, their creation remains challenging, and many rare diseases lack approved therapies. Therefore, drug repurposing has emerged as a viable strategy for identifying potential new treatments for these pathologies. A technique that consists in using existing drugs to treat a new disease different from the one that they were developed. This approach can significantly reduce the time and cost of drug development while increasing the likelihood of success. In this paper, we examined the temporal progression of orphan drugs since their introduction and assess the impact of drug repositioning on treatments for rare diseases. Additionally, we aim to identify biological patterns that may be unique to rare diseases treated with repurposed orphan drugs. To this end, we analyzed various biological components associated with these diseases, categorized linked diseases, and obtained the type of orphan drug associated with them. Lastly, we evaluated the phenotypic similarity between diseases treated with an orphan drug through repurposing. Through these findings, we have gained insight into the evolution of orphan drug development in recent years and identified specific patterns that characterize rare diseases associated with them.

OBJECTIVE: Artificial intelligence (AI) models may propagate harmful biases in performance and hence negatively affect the underserved. We aimed to assess the degree to which data quality of electronic health records (EHRs) affected by inequities related to low socioeconomic status (SES), results in differential performance of AI models across SES. MATERIALS AND METHODS: This study utilized existing machine learning models for predicting asthma exacerbation in children with asthma. We compared balanced error rate (BER) against different SES levels measured by HOUsing-based SocioEconomic Status measure (HOUSES) index. As a possible mechanism for differential performance, we also compared incompleteness of EHR information relevant to asthma care by SES. RESULTS: Asthmatic children with lower SES had larger BER than those with higher SES (eg, ratio = 1.35 for HOUSES Q1 vs Q2-Q4) and had a higher proportion of missing information relevant to asthma care (eg, 41% vs 24% for missing asthma severity and 12% vs 9.8% for undiagnosed asthma despite meeting asthma criteria). DISCUSSION: Our study suggests that lower SES is associated with worse predictive model performance. It also highlights the potential role of incomplete EHR data in this differential performance and suggests a way to mitigate this bias. CONCLUSION: The HOUSES index allows AI researchers to assess bias in predictive model performance by SES. Although our case study was based on a small sample size and a single-site study, the study results highlight a potential strategy for identifying bias by using an innovative SES measure.

OBJECTIVE: Electronic health record documentation by intensive care unit (ICU) clinicians may predict patient outcomes. However, it is unclear whether physician and nursing notes differ in their ability to predict short-term ICU prognosis. We aimed to investigate and compare the ability of physician and nursing notes, written in the first 48 hours of admission, to predict ICU length of stay and mortality using 3 analytical methods. MATERIALS AND METHODS: This was a retrospective cohort study with split sampling for model training and testing. We included patients ≥18 years of age admitted to the ICU at Beth Israel Deaconess Medical Center in Boston, Massachusetts, from 2008 to 2012. Physician or nursing notes generated within the first 48 hours of admission were used with standard machine learning methods to predict outcomes. RESULTS: For the primary outcome of composite score of ICU length of stay ≥7 days or in-hospital mortality, the gradient boosting model had better performance than the logistic regression and random forest models. Nursing and physician notes achieved area under the curves (AUCs) of 0.826 and 0.796, respectively, with even better predictive power when combined (AUC, 0.839). DISCUSSION: Models using only nursing notes more accurately predicted short-term prognosis than did models using only physician notes, but in combination, the models achieved the greatest accuracy in prediction. CONCLUSIONS: Our findings demonstrate that statistical models derived from text analysis in the first 48 hours of ICU admission can predict patient outcomes. Physicians' and nurses' notes are both uniquely important in mortality prediction and combining these notes can produce a better predictive model.

OBJECTIVE: We aimed to develop a model for accurate prediction of general care inpatient deterioration. MATERIALS AND METHODS: Training and internal validation datasets were built using 2-year data from a quaternary hospital in the Midwest. Model training used gradient boosting and feature engineering (clinically relevant interactions, time-series information) to predict general care inpatient deterioration (resuscitation call, intensive care unit transfer, or rapid response team call) in 24 hours. Data from a tertiary care hospital in the Southwest were used for external validation. C-statistic, sensitivity, positive predictive value, and alert rate were calculated for different cutoffs and compared with the National Early Warning Score. Sensitivity analysis evaluated prediction of intensive care unit transfer or resuscitation call. RESULTS: Training, internal validation, and external validation datasets included 24 500, 25 784 and 53 956 hospitalizations, respectively. The Mayo Clinic Early Warning Score (MC-EWS) demonstrated excellent discrimination in both the internal and external validation datasets (C-statistic = 0.913, 0.937, respectively), and results were consistent in the sensitivity analysis (C-statistic = 0.932 in external validation). At a sensitivity of 73%, MC-EWS would generate 0.7 alerts per day per 10 patients, 45% less than the National Early Warning Score. DISCUSSION: Low alert rates are important for implementation of an alert system. Other early warning scores developed for the general care ward have achieved lower discrimination overall compared with MC-EWS, likely because MC-EWS includes both nursing assessments and extensive feature engineering. CONCLUSIONS: MC-EWS achieved superior prediction of general care inpatient deterioration using sophisticated feature engineering and a machine learning approach, reducing alert rate.

Hospital census prediction has well-described implications for efficient hospital resource utilization, and recent issues with hospital crowding due to CoVID-19 have emphasized the importance of this task. Our team has been leading an institutional effort to develop machine-learning models that can predict hospital census 12 hours into the future. We describe our efforts at developing accurate empirical models for this task. Ultimately, with limited resources and time, we were able to develop simple yet useful models for 12-hour census prediction and design a dashboard application to display this output to our hospital's decision-makers. Specifically, we found that linear models with ElasticNet regularization performed well for this task with relative 95% error of +/- 3.4% and that this work could be completed in approximately 7 months.