Dataset Information

Project IDentif.AI: Harnessing Artificial Intelligence to Rapidly Optimize Combination Therapy Development for Infectious Disease Intervention.

ABSTRACT: In 2019/2020, the emergence of coronavirus disease 2019 (COVID-19) resulted in rapid increases in infection rates as well as patient mortality. Treatment options addressing COVID-19 included drug repurposing, investigational therapies such as remdesivir, and vaccine development. Combination therapy based on drug repurposing is among the most widely pursued of these efforts. Multi-drug regimens are traditionally designed by selecting drugs based on their mechanism of action. This is followed by dose-finding to achieve drug synergy. This approach is widely-used for drug development and repurposing. Realizing synergistic combinations, however, is a substantially different outcome compared to globally optimizing combination therapy, which realizes the best possible treatment outcome by a set of candidate therapies and doses toward a disease indication. To address this challenge, the results of Project IDentif.AI (Identifying Infectious Disease Combination Therapy with Artificial Intelligence) are reported. An AI-based platform is used to interrogate a massive 12 drug/dose parameter space, rapidly identifying actionable combination therapies that optimally inhibit A549 lung cell infection by vesicular stomatitis virus within three days of project start. Importantly, a sevenfold difference in efficacy is observed between the top-ranked combination being optimally and sub-optimally dosed, demonstrating the critical importance of ideal drug and dose identification. This platform is disease indication and disease mechanism-agnostic, and potentially applicable to the systematic N-of-1 and population-wide design of highly efficacious and tolerable clinical regimens. This work also discusses key factors ranging from healthcare economics to global health policy that may serve to drive the broader deployment of this platform to address COVID-19 and future pandemics.

SUBMITTER: Abdulla A

PROVIDER: S-EPMC7235487 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Project IDentif.AI: Harnessing Artificial Intelligence to Rapidly Optimize Combination Therapy Development for Infectious Disease Intervention.

Abdulla Aynur A Wang Boqian B Qian Feng F Kee Theodore T Blasiak Agata A Ong Yoong Hun YH Hooi Lissa L Parekh Falgunee F Soriano Rafael R Olinger Gene G GG Keppo Jussi J Hardesty Chris L CL Chow Edward K EK Ho Dean D Ding Xianting X

Advanced therapeutics 20200416 7

In 2019/2020, the emergence of coronavirus disease 2019 (COVID-19) resulted in rapid increases in infection rates as well as patient mortality. Treatment options addressing COVID-19 included drug repurposing, investigational therapies such as remdesivir, and vaccine development. Combination therapy based on drug repurposing is among the most widely pursued of these efforts. Multi-drug regimens are traditionally designed by selecting drugs based on their mechanism of action. This is followed by d ...[more]

PMID: 32838027

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Project description:BackgroundBehaviour change is key to addressing both the challenges facing human health and wellbeing and to promoting the uptake of research findings in health policy and practice. We need to make better use of the vast amount of accumulating evidence from behaviour change intervention (BCI) evaluations and promote the uptake of that evidence into a wide range of contexts. The scale and complexity of the task of synthesising and interpreting this evidence, and increasing evidence timeliness and accessibility, will require increased computer support. The Human Behaviour-Change Project (HBCP) will use Artificial Intelligence and Machine Learning to (i) develop and evaluate a 'Knowledge System' that automatically extracts, synthesises and interprets findings from BCI evaluation reports to generate new insights about behaviour change and improve prediction of intervention effectiveness and (ii) allow users, such as practitioners, policy makers and researchers, to easily and efficiently query the system to get answers to variants of the question 'What works, compared with what, how well, with what exposure, with what behaviours (for how long), for whom, in what settings and why?'.MethodsThe HBCP will: a) develop an ontology of BCI evaluations and their reports linking effect sizes for given target behaviours with intervention content and delivery and mechanisms of action, as moderated by exposure, populations and settings; b) develop and train an automated feature extraction system to annotate BCI evaluation reports using this ontology; c) develop and train machine learning and reasoning algorithms to use the annotated BCI evaluation reports to predict effect sizes for particular combinations of behaviours, interventions, populations and settings; d) build user and machine interfaces for interrogating and updating the knowledge base; and e) evaluate all the above in terms of performance and utility.DiscussionThe HBCP aims to revolutionise our ability to synthesise, interpret and deliver evidence on behaviour change interventions that is up-to-date and tailored to user need and context. This will enhance the usefulness, and support the implementation of, that evidence.

Project description:ImportancePhysicians are required to work with rapidly growing amounts of medical data. Approximately 62% of time per patient is devoted to reviewing electronic health records (EHRs), with clinical data review being the most time-consuming portion.ObjectiveTo determine whether an artificial intelligence (AI) system developed to organize and display new patient referral records would improve a clinician's ability to extract patient information compared with the current standard of care.Design, setting, and participantsIn this prognostic study, an AI system was created to organize patient records and improve data retrieval. To evaluate the system on time and accuracy, a nonblinded, prospective study was conducted at a single academic medical center. Recruitment emails were sent to all physicians in the gastroenterology division, and 12 clinicians agreed to participate. Each of the clinicians participating in the study received 2 referral records: 1 AI-optimized patient record and 1 standard (non-AI-optimized) patient record. For each record, clinicians were asked 22 questions requiring them to search the assigned record for clinically relevant information. Clinicians reviewed records from June 1 to August 30, 2020.Main outcomes and measuresThe time required to answer each question, along with accuracy, was measured for both records, with and without AI optimization. Participants were asked to assess overall satisfaction with the AI system, their preferred review method (AI-optimized vs standard), and other topics to assess clinical utility.ResultsTwelve gastroenterology physicians/fellows completed the study. Compared with standard (non-AI-optimized) patient record review, the AI system saved first-time physician users 18% of the time used to answer the clinical questions (10.5 [95% CI, 8.5-12.6] vs 12.8 [95% CI, 9.4-16.2] minutes; P = .02). There was no significant decrease in accuracy when physicians retrieved important patient information (83.7% [95% CI, 79.3%-88.2%] with the AI-optimized vs 86.0% [95% CI, 81.8%-90.2%] without the AI-optimized record; P = .81). Survey responses from physicians were generally positive across all questions. Eleven of 12 physicians (92%) preferred the AI-optimized record review to standard review. Despite a learning curve pointed out by respondents, 11 of 12 physicians believed that the technology would save them time to assess new patient records and were interested in using this technology in their clinic.Conclusions and relevanceIn this prognostic study, an AI system helped physicians extract relevant patient information in a shorter time while maintaining high accuracy. This finding is particularly germane to the ever-increasing amounts of medical data and increased stressors on clinicians. Increased user familiarity with the AI system, along with further enhancements in the system itself, hold promise to further improve physician data extraction from large quantities of patient health records.

Project description:ImportanceInpatient clinical deterioration is associated with substantial morbidity and mortality but may be easily missed by clinicians. Early warning scores have been developed to alert clinicians to patients at high risk of clinical deterioration, but there is limited evidence for their effectiveness.ObjectiveTo evaluate the effectiveness of an artificial intelligence deterioration model-enabled intervention to reduce the risk of escalations in care among hospitalized patients using a study design that facilitates stronger causal inference.Design, setting, and participantsThis cohort study used a regression discontinuity design that controlled for confounding and was based on Epic Deterioration Index (EDI; Epic Systems Corporation) prediction model scores. Compared with other observational research, the regression discontinuity design facilitates causal analysis. Hospitalized adults were included from 4 general internal medicine units in 1 academic hospital from January 17, 2021, through November 16, 2022.ExposureAn artificial intelligence deterioration model-enabled intervention, consisting of alerts based on an EDI score threshold with an associated collaborative workflow among nurses and physicians.Main outcomes and measuresThe primary outcome was escalations in care, including rapid response team activation, transfer to the intensive care unit, or cardiopulmonary arrest during hospitalization.ResultsDuring the study, 9938 patients were admitted to 1 of the 4 units, with 963 patients (median [IQR] age, 76.1 [64.2-86.2] years; 498 males [52.3%]) included within the primary regression discontinuity analysis. The median (IQR) Elixhauser Comorbidity Index score in the primary analysis cohort was 10 (0-24). The intervention was associated with a -10.4-percentage point (95% CI, -20.1 to -0.8 percentage points; P = .03) absolute risk reduction in the primary outcome for patients at the EDI score threshold. There was no evidence of a discontinuity in measured confounders at the EDI score threshold.Conclusions and relevanceUsing a regression discontinuity design, this cohort study found that the implementation of an artificial intelligence deterioration model-enabled intervention was associated with a significantly decreased risk of escalations in care among inpatients. These results provide evidence for the effectiveness of this intervention and support its further expansion and testing in other care settings.

Project description:BackgroundEach year, millions of Americans receive evidence-based psychotherapies (EBPs) like cognitive behavioral therapy (CBT) for the treatment of mental and behavioral health problems. Yet, at present, there is no scalable method for evaluating the quality of psychotherapy services, leaving EBP quality and effectiveness largely unmeasured and unknown. Project AFFECT will develop and evaluate an AI-based software system to automatically estimate CBT fidelity from a recording of a CBT session. Project AFFECT is an NIMH-funded research partnership between the Penn Collaborative for CBT and Implementation Science and Lyssn.io, Inc. ("Lyssn") a start-up developing AI-based technologies that are objective, scalable, and cost efficient, to support training, supervision, and quality assurance of EBPs. Lyssn provides HIPAA-compliant, cloud-based software for secure recording, sharing, and reviewing of therapy sessions, which includes AI-generated metrics for CBT. The proposed tool will build from and be integrated into this core platform.MethodsPhase I will work from an existing software prototype to develop a LyssnCBT user interface geared to the needs of community mental health (CMH) agencies. Core activities include a user-centered design focus group and interviews with community mental health therapists, supervisors, and administrators to inform the design and development of LyssnCBT. LyssnCBT will be evaluated for usability and implementation readiness in a final stage of Phase I. Phase II will conduct a stepped-wedge, hybrid implementation-effectiveness randomized trial (N = 1,875 clients) to evaluate the effectiveness of LyssnCBT to improve therapist CBT skills and client outcomes and reduce client drop-out. Analyses will also examine the hypothesized mechanism of action underlying LyssnCBT.DiscussionSuccessful execution will provide automated, scalable CBT fidelity feedback for the first time ever, supporting high-quality training, supervision, and quality assurance, and providing a core technology foundation that could support the quality delivery of a range of EBPs in the future.Trial registrationClinicalTrials.gov; NCT05340738 ; approved 4/21/2022.

Dataset Information

Project IDentif.AI: Harnessing Artificial Intelligence to Rapidly Optimize Combination Therapy Development for Infectious Disease Intervention.

Publications

Project IDentif.AI: Harnessing Artificial Intelligence to Rapidly Optimize Combination Therapy Development for Infectious Disease Intervention.

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