Outlier analysis for accelerating clinical discovery: An augmented intelligence framework and a systematic review.

Clinical discoveries largely depend on dedicated clinicians and scientists to identify and pursue unique and unusual clinical encounters with patients and communicate these through case reports and case series. This process has remained essentially unchanged throughout the history of modern medicine. However, these traditional methods are inefficient, especially considering the modern-day availability of health-related data and the sophistication of computer processing. Outlier analysis has been used in various fields to uncover unique observations, including fraud detection in finance and quality control in manufacturing. We propose that clinical discovery can be formulated as an outlier problem within an augmented intelligence framework to be implemented on any health-related data. Such an augmented intelligence approach would accelerate the identification and pursuit of clinical discoveries, advancing our medical knowledge and uncovering new therapies and management approaches. We define clinical discoveries as contextual outliers measured through an information-based approach and with a novelty-based root cause. Our augmented intelligence framework has five steps: define a patient population with a desired clinical outcome, build a predictive model, identify outliers through appropriate measures, investigate outliers through domain content experts, and generate scientific hypotheses. Recognizing that the field of obstetrics can particularly benefit from this approach, as it is traditionally neglected in commercial research, we conducted a systematic review to explore how outlier analysis is implemented in obstetric research. We identified two obstetrics-related studies that assessed outliers at an aggregate level for purposes outside of clinical discovery. Our findings indicate that using outlier analysis in clinical research in obstetrics and clinical research, in general, requires further development.

Augmented Intelligence for Clinical Discovery in Hypertensive Disorders of Pregnancy Using Outlier Analysis.

Objectives Clinical discoveries are heralded by observing unique and unusual clinical cases. The effort of identifying such cases rests on the shoulders of busy clinicians. We assess the feasibility and applicability of an augmented intelligence framework to accelerate the rate of clinical discovery in preeclampsia and hypertensive disorders of pregnancy-an area that has seen little change in its clinical management. Methods We conducted a retrospective exploratory outlier analysis of participants enrolled in the folic acid clinical trial (FACT, N=2,301) and the Ottawa and Kingston birth cohort (OaK, N=8,085). We applied two outlier analysis methods: extreme misclassification contextual outlier and isolation forest point outlier. The extreme misclassification contextual outlier is based on a random forest predictive model for the outcome of preeclampsia in FACT and hypertensive disorder of pregnancy in OaK. We defined outliers in the extreme misclassification approach as mislabelled observations with a confidence level of more than 90%. Within the isolation forest approach, we defined outliers as observations with an average path length z score less or equal to -3, or more or equal to 3. Content experts reviewed the identified outliers and determined if they represented a potential novelty that could conceivably lead to a clinical discovery. Results In the FACT study, we identified 19 outliers using the isolation forest algorithm and 13 outliers using the random forest extreme misclassification approach. We determined that three (15.8%) and 10 (76.9%) were potential novelties, respectively. Out of 8,085 participants in the OaK study, we identified 172 outliers using the isolation forest algorithm and 98 outliers using the random forest extreme misclassification approach; four (2.3%) and 32 (32.7%), respectively, were potential novelties. Overall, the outlier analysis part of the augmented intelligence framework identified a total of 302 outliers. These were subsequently reviewed by content experts, representing the human part of the augmented intelligence framework. The clinical review determined that 49 of the 302 outliers represented potential novelties.  Conclusions Augmented intelligence using extreme misclassification outlier analysis is a feasible and applicable approach for accelerating the rate of clinical discoveries. The use of an extreme misclassification contextual outlier analysis approach has resulted in a higher proportion of potential novelties than using the more traditional point outlier isolation forest approach. This finding was consistent in both the clinical trial and real-world cohort study data. Using augmented intelligence through outlier analysis has the potential to speed up the process of identifying potential clinical discoveries. This approach can be replicated across clinical disciplines and could exist within electronic medical records systems to automatically identify outliers within clinical notes to clinical experts.

Do Case Reports and Case Series Generate Clinical Discoveries About Preeclampsia? A Systematic Review.

Background: Preeclampsia is a leading cause of maternal and perinatal mortality and morbidity. The management of preeclampsia has not changed much in more than two decades, and its aetiology is still not fully understood. Case reports and case series have traditionally been used to communicate new knowledge about existing conditions. Whether this is true for preeclampsia is not known. Objective: To determine whether recent case reports or case series have generated new knowledge and clinical discoveries about preeclampsia. Methods: A detailed search strategy was developed in consultation with a medical librarian. Two bibliographic databases were searched through Ovid: Embase and MEDLINE. We selected case reports or case series published between 2015 and 2020, comprising pregnant persons diagnosed with hypertensive disorders of pregnancy, including preeclampsia. Two reviewers independently screened all publications. One reviewer extracted data from included studies, while another conducted a quality check of extracted data. We developed a codebook to guide our data extraction and outcomes assessment. The quality of each report was determined based on Joanna Briggs Institute (JBI) critical appraisal checklist for case reports and case series. Results: We included 104 case reports and three case series, together comprising 118 pregnancies. A severe presentation or complication of preeclampsia was reported in 81% of pregnancies, and 84% had a positive maternal outcome, free of death or persistent complications. Only 8% of the case reports were deemed to be of high quality, and 53.8% of moderate quality; none of the case series were of high quality. A total of 26 of the 107 publications (24.3%) included a novel clinical discovery as a central theme. Conclusion: Over two-thirds of recent case reports and case series about preeclampsia do not appear to present new knowledge or discoveries about preeclampsia, and most are of low quality.

Changing Health-Related Behaviors 6: Analysis, Interpretation, and Application of Big Data.

The behavior of individuals can affect both their own health and the health of those around them. Furthermore, the behavior of healthcare providers obviously affects the health of those receiving the care. In both of these cases, and in spite of its known benefits, behavior change is difficult for most people. To make change easier, big data can provide insight through an objective and nonjudgmental perspective. It may also help make specific, individualized, evidence-based recommendations for effective change. We provide a historical perspective on data and health and then describe the value of adding big data systems and how they are implemented. We discuss some of the sources of big data and how it is collected. We also review the additional challenges for analysis, interpretation, and application of big data that require specific technologies. We end with a summary of current uses of big data for behavior change and suggestions for additional approaches, which may be of benefit.

An ontology-driven framework to support the dynamic formation of an interdisciplinary healthcare team.

BACKGROUND AND PURPOSE: Teamwork has become a modus operandi in healthcare and delivery of patient care by an interdisciplinary healthcare team (IHT) is now a prevailing modality of care. We argue that a formal and automated support framework is needed for an IHT to properly leverage information technology resources. Such a framework should allow for patient preferences and expand a representation of a clinical workflow with a formal model of dynamic formation of a team, especially with regards to team leader- and membership, and the assignment of tasks to team members. Our goal was to develop such a support framework, present its prototype software implementation and verify the implementation using a proof-of-concept use case. Specifically, we focused on clinical workflows for in-patient tertiary care and on patient preferences with regards to selecting team members and team leaders. MATERIALS AND METHODS: Drawing on the research on clinical teamwork we defined the conceptual foundations for the proposed framework. Then, we designed its architecture and used ontology-driven design and first-order logic with associated reasoning methods to create and operationalize architectural elements. Finally, we incorporated existing solutions for business workflow modeling and execution as a backend for implementing the proposed framework. RESULTS: We developed a Team and Workflow Management Framework (TWMF) with semantic components that allow for formalizing and operationalizing team formation in in-patient tertiary care setting and support provider-related patient preferences. We also created a prototype software implementation of TWMF using the IBM Business Process Manager platform. This implementation was evaluated in several simulated patient scenarios. CONCLUSIONS: TWMF integrates existing workflow technologies and extends them with the capabilities to support dynamic formation of an IHT. Results of this research can be used to support real-time execution of clinical workflows, or to simulate their execution in order to assess the impact of various conditions (e.g., patterns of work shifts, staffing) on IHT operations.

CEA: Clinical Event Annotator mHealth Application for Real-time Patient Monitoring.

This research develops a novel dynamic mobile health (mHealth) application (app), called the Clinical Event Annotator (CEA). The CEA comprises of a native Android tablet app and an administrative web app. The native app is used at the patient bedside to manually annotate clinical events in real-time. Event types include patient monitor alarms, routine care, clinical interventions, and patient movements. The app can be dynamically updated with user-defined customized events. The web app generates reports of the annotation sessions. The CEA app is developed to support a clinical study that explores the use of pressure-sensitive mats (PSM) in the neonatal intensive care unit (NICU) to detect the respiratory rate (RR), heart rate (HR), and movement of critically ill neonatal patients. High-fidelity CEA app annotations are synced with a backend database that enables integration and synchronization with independently acquired patient monitoring data, such as RR, HR, and contact pressure data from the PSM. The gold standard CEA annotations serve the purpose of retrospectively training machine learning algorithms for clinical event detection. Preliminary test results from use of the app in the clinical study are presented. Development of the CEA app is a unique and novel contribution that addresses the well-known problem of manually annotating physiologic data streams to support clinical data mining applications.

A real-time dashboard for managing pathology processes.

CONTEXT: The Eastern Ontario Regional Laboratory Association (EORLA) is a newly established association of all the laboratory and pathology departments of Eastern Ontario that currently includes facilities from eight hospitals. All surgical specimens for EORLA are processed in one central location, the Department of Pathology and Laboratory Medicine (DPLM) at The Ottawa Hospital (TOH), where the rapid growth and influx of surgical and cytology specimens has created many challenges in ensuring the timely processing of cases and reports. Although the entire process is maintained and tracked in a clinical information system, this system lacks pre-emptive warnings that can help management address issues as they arise. AIMS: Dashboard technology provides automated, real-time visual clues that could be used to alert management when a case or specimen is not being processed within predefined time frames. We describe the development of a dashboard helping pathology clinical management to make informed decisions on specimen allocation and tracking. METHODS: The dashboard was designed and developed in two phases, following a prototyping approach. The first prototype of the dashboard helped monitor and manage pathology processes at the DPLM. RESULTS: The use of this dashboard helped to uncover operational inefficiencies and contributed to an improvement of turn-around time within The Ottawa Hospital's DPML. It also allowed the discovery of additional requirements, leading to a second prototype that provides finer-grained, real-time information about individual cases and specimens. CONCLUSION: We successfully developed a dashboard that enables managers to address delays and bottlenecks in specimen allocation and tracking. This support ensures that pathology reports are provided within time frame standards required for high-quality patient care. Given the importance of rapid diagnostics for a number of diseases, the use of real-time dashboards within pathology departments could contribute to improving the quality of patient care beyond EORLA's.