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This prospective phase II clinical trial (Side Out 2) explored the clinical benefits of treatment selection informed by multi‐omic molecular profiling (MoMP) in refractory metastatic breast cancers (MBCs). Core needle biopsies were collected from 32 patients with MBC at trial enrollment. Patients had received an average of 3.94 previous lines of treatment in the metastatic setting before enrollment in this study. Samples underwent MoMP, including exome sequencing, RNA sequencing (RNA‐Seq), immunohistochemistry, and quantitative protein pathway activation mapping by Reverse Phase Protein Microarray (RPPA). Clinical benefit was assessed using the previously published growth modulation index (GMI) under the hypothesis that MoMP‐selected therapy would warrant further investigation for GMI ≥ 1.3 in ≥ 35% of the patients. Of the 32 patients enrolled, 29 received treatment based on their MoMP and 25 met the follow‐up criteria established by the trial protocol. Molecular information was delivered to the tumor board in a median time frame of 14 days (11–22 days), and targetable alterations for commercially available agents were found in 23/25 patients (92%). Of the 25 patients, 14 (56%) reached GMI ≥ 1.3. A high level of DNA topoisomerase I (TOPO1) led to the selection of irinotecan‐based treatments in 48% (12/25) of the patients. A pooled analysis suggested clinical benefit in patients with high TOPO1 expression receiving irinotecan‐based regimens (GMI ≥ 1.3 in 66.7% of cases). These results confirmed previous observations that MoMP increases the frequency of identifiable actionable alterations (92% of patients). The MoMP proposed allows the identification of biomarkers that are frequently expressed in MBCs and the evaluation of their role as predictors of response to commercially available agents. Lastly, this study confirmed the role of MoMP for informing treatment selection in refractory MBC patients: more than half of the enrolled patients reached a GMI ≥ 1.3 even after multiple lines of previous therapies for metastatic disease.

Abstract Background Assessment of functional ability, including activities of daily living (ADLs), is a manual process completed by skilled health professionals. In the presented research, an automated decision support tool, the Computational Barthel Index Tool (CBIT), was constructed that can automatically assess and predict probabilities of current and future ADLs based on patients’ medical history. Methods The data used to construct the tool include the demographic information, inpatient and outpatient diagnosis codes, and reported disabilities of 181,213 residents of the Department of Veterans Affairs’ (VA) Community Living Centers. Supervised machine learning methods were applied to construct the CBIT. Temporal information about times from the first and the most recent occurrence of diagnoses was encoded. Ten-fold cross-validation was used to tune hyperparameters, and independent test sets were used to evaluate models using AUC, accuracy, recall and precision. Random forest achieved the best model quality. Models were calibrated using isotonic regression. Results The unabridged version of CBIT uses 578 patient characteristics and achieved average AUC of 0.94 (0.93–0.95), accuracy of 0.90 (0.89–0.91), precision of 0.91 (0.89–0.92), and recall of 0.90 (0.84–0.95) when re-evaluating patients. CBIT is also capable of predicting ADLs up to one year ahead, with accuracy decreasing over time, giving average AUC of 0.77 (0.73–0.79), accuracy of 0.73 (0.69–0.80), precision of 0.74 (0.66–0.81), and recall of 0.69 (0.34–0.96). A simplified version of CBIT with 50 top patient characteristics reached performance that does not significantly differ from full CBIT. Conclusion Discharge planners, disability application reviewers and clinicians evaluating comparative effectiveness of treatments can use CBIT to assess and predict information on functional status of patients.

This study uses two existing data sources to examine how patients' symptoms can be used to differentiate COVID-19 from other respiratory diseases. One dataset consisted of 839,288 laboratory-confirmed, symptomatic, COVID-19 positive cases reported to the Centers for Disease Control and Prevention (CDC) from March 1, 2019, to September 30, 2020. The second dataset provided the controls and included 1,814 laboratory-confirmed influenza positive, symptomatic cases, and 812 cases with symptomatic influenza-like-illnesses. The controls were reported to the Influenza Research Database of the National Institute of Allergy and Infectious Diseases (NIAID) between January 1, 2000, and December 30, 2018. Data were analyzed using case-control study design. The comparisons were done using 45 scenarios, with each scenario making different assumptions regarding prevalence of COVID-19 (2%, 4%, and 6%), influenza (0.01%, 3%, 6%, 9%, 12%) and influenza-like-illnesses (1%, 3.5% and 7%). For each scenario, a logistic regression model was used to predict COVID-19 from 2 demographic variables (age, gender) and 10 symptoms (cough, fever, chills, diarrhea, nausea and vomiting, shortness of breath, runny nose, sore throat, myalgia, and headache). The 5-fold cross-validated Area under the Receiver Operating Curves (AROC) was used to report the accuracy of these regression models. The value of various symptoms in differentiating COVID-19 from influenza depended on a variety of factors, including (1) prevalence of pathogens that cause COVID-19, influenza, and influenza-like-illness; (2) age of the patient, and (3) presence of other symptoms. The model that relied on 5-way combination of symptoms and demographic variables, age and gender, had a cross-validated AROC of 90%, suggesting that it could accurately differentiate influenza from COVID-19. This model, however, is too complex to be used in clinical practice without relying on computer-based decision aid. Study results encourage development of web-based, stand-alone, artificial Intelligence model that can interview patients and help clinicians make quarantine and triage decisions.

Abstract Background Bio-ontologies are becoming increasingly important in knowledge representation and in the machine learning (ML) fields. This paper presents a ML approach that incorporates bio-ontologies and its application to the SEER-MHOS dataset to discover patterns of patient characteristics that impact the ability to perform activities of daily living (ADLs). Bio-ontologies are used to provide computable knowledge for ML methods to “understand” biomedical data. Results This retrospective study included 723 cancer patients from the SEER-MHOS dataset. Two ML methods were applied to create predictive models for ADL disabilities for the first year after a patient’s cancer diagnosis. The first method is a standard rule learning algorithm; the second is that same algorithm additionally equipped with methods for reasoning with ontologies. The models showed that a patient’s race, ethnicity, smoking preference, treatment plan and tumor characteristics including histology, staging, cancer site, and morphology were predictors for ADL performance levels one year after cancer diagnosis. The ontology-guided ML method was more accurate at predicting ADL performance levels (P

The task identifying changes and irregularities in medical insurance claim pay-ments is a difficult process of which the traditional practice involves queryinghistorical claims databases and flagging potential claims as normal or abnor-mal. Because what is considered as normal payment is usually unknown andmay change over time, abnormal payments often pass undetected; only to bediscovered when the payment period has passed.This paper presents the problem of on-line unsupervised learning from datastreams when the distribution that generates the data changes or drifts overtime. Automated algorithms for detecting drifting concepts in a probabilitydistribution of the data are presented. The idea behind the presented driftdetection methods is to transform the distribution of the data within a slidingwindow into a more convenient distribution. Then, a test statistics p-value ata given significance level can be used to infer the drift rate, adjust the windowsize and decide on the status of the drift. The detected concepts drifts areused to label the data, for subsequent learning of classification models by asupervised learner. The algorithms were tested on several synthetic and realmedical claims data sets.