Background The systemic treatment of cancer typically requires the use of multiple anticancer agents in combination or sequentially. Clinical narrative texts often contain extensive descriptions of the temporal sequencing of systemic anticancer therapy (SACT), setting up an important task that may be amenable to automated extraction of SACT timelines. Objective We aimed to explore automatic methods for extracting patient-level SACT timelines from clinical narratives in the electronic medical records (EMRs). Methods We used two datasets from two institutions: (1) a colorectal cancer (CRC) dataset including the entire EMR of the 199 patients in the THYME (Temporal Histories of Your Medical Event) dataset and (2) the 2024 ChemoTimelines shared task dataset including 149 patients with ovarian cancer, breast cancer, and melanoma. We explored finetuning smaller language models trained to attend to events and time expressions, and few-shot prompting of large language models (LLMs). Evaluation used the 2024 ChemoTimelines shared task configuration—Subtask1 involving the construction of SACT timelines from manually annotated SACT event and time expression mentions provided as input in addition to the patient’s notes and Subtask2 requiring extraction of SACT timelines directly from the patient’s notes. Results Our task-specific finetuned EntityBERT model achieved 93% F1-score, outperforming the best results in Subtask1 of the 2024 ChemoTimelines shared task (90%). It ranked second in Subtask2. LLM (LLaMA2, LLaMA3.1, and Mixtral) performance lagged the task-specific finetuned model performance for both the THYME and shared task datasets. On the shared task datasets, the best LLM performance was 77% macro F1-score, 16% points lower than the task-specific finetuned system (Subtask1). Conclusions In this paper, we explored approaches for patient-level timeline extraction through the SACT timeline extraction task. Our results and analysis add to the knowledge of extracting treatment timelines from EMR clinical narratives using language modeling methods.

ObjectiveTo use software, datasets, and data formats in the domain of Infectious Disease Epidemiology as a test collection to evaluate a novel M1 use case, which we introduce in this paper. M1 is a machine that upon receipt of a new digital object of research, exhaustively finds all valid compositions of it with existing objects.MethodWe implemented a data-format-matching-only M1 using exhaustive search, which we refer to as M1DFM. We then ran M1DFM on the test collection and used error analysis to identify needed semantic constraints.ResultsPrecision of M1DFM search was 61.7%. Error analysis identified needed semantic constraints and needed changes in handling of data services. Most semantic constraints were simple, but one data format was sufficiently complex to be practically impossible to represent semantic constraints over, from which we conclude limitatively that software developers will have to meet the machines halfway by engineering software whose inputs are sufficiently simple that their semantic constraints can be represented, akin to the simple APIs of services. We summarize these insights as M1-FAIR guiding principles for composability and suggest a roadmap for progressively capable devices in the service of reuse and accelerated scientific discovery.ConclusionAlgorithmic search of digital repositories for valid workflow compositions has potential to accelerate scientific discovery but requires a scalable solution to the problem of knowledge acquisition about semantic constraints on software inputs. Additionally, practical limitations on the logical complexity of semantic constraints must be respected, which has implications for the design of software.

BACKGROUND:Coronavirus Disease 2019 (COVID-19) continues to cause significant hospitalizations and deaths in the United States. Its continued burden and the impact of annually reformulated vaccines remain unclear. Here, we present projections of COVID-19 hospitalizations and deaths in the United States for the next 2 years under 2 plausible assumptions about immune escape (20% per year and 50% per year) and 3 possible CDC recommendations for the use of annually reformulated vaccines (no recommendation, vaccination for those aged 65 years and over, vaccination for all eligible age groups based on FDA approval). METHODS AND FINDINGS:The COVID-19 Scenario Modeling Hub solicited projections of COVID-19 hospitalization and deaths between April 15, 2023 and April 15, 2025 under 6 scenarios representing the intersection of considered levels of immune escape and vaccination. Annually reformulated vaccines are assumed to be 65% effective against symptomatic infection with strains circulating on June 15 of each year and to become available on September 1. Age- and state-specific coverage in recommended groups was assumed to match that seen for the first (fall 2021) COVID-19 booster. State and national projections from 8 modeling teams were ensembled to produce projections for each scenario and expected reductions in disease outcomes due to vaccination over the projection period. From April 15, 2023 to April 15, 2025, COVID-19 is projected to cause annual epidemics peaking November to January. In the most pessimistic scenario (high immune escape, no vaccination recommendation), we project 2.1 million (90% projection interval (PI) [1,438,000, 4,270,000]) hospitalizations and 209,000 (90% PI [139,000, 461,000]) deaths, exceeding pre-pandemic mortality of influenza and pneumonia. In high immune escape scenarios, vaccination of those aged 65+ results in 230,000 (95% confidence interval (CI) [104,000, 355,000]) fewer hospitalizations and 33,000 (95% CI [12,000, 54,000]) fewer deaths, while vaccination of all eligible individuals results in 431,000 (95% CI: 264,000-598,000) fewer hospitalizations and 49,000 (95% CI [29,000, 69,000]) fewer deaths. CONCLUSIONS:COVID-19 is projected to be a significant public health threat over the coming 2 years. Broad vaccination has the potential to substantially reduce the burden of this disease, saving tens of thousands of lives each year.

Our ability to forecast epidemics more than a few weeks into the future is constrained by the complexity of disease systems, our limited ability to measure the current state of an epidemic, and uncertainties in how human action will affect transmission. Realistic longer-term projections (spanning more than a few weeks) may, however, be possible under defined scenarios that specify the future state of critical epidemic drivers, with the additional benefit that such scenarios can be used to anticipate the comparative effect of control measures. Since December 2020, the U.S. COVID-19 Scenario Modeling Hub (SMH) has convened multiple modeling teams to make 6-month ahead projections of the number of SARS-CoV-2 cases, hospitalizations and deaths. The SMH released nearly 1.8 million national and state-level projections between February 2021 and November 2022. SMH performance varied widely as a function of both scenario validity and model calibration. Scenario assumptions were periodically invalidated by the arrival of unanticipated SARS-CoV-2 variants, but SMH still provided projections on average 22 weeks before changes in assumptions (such as virus transmissibility) invalidated scenarios and their corresponding projections. During these periods, before emergence of a novel variant, a linear opinion pool ensemble of contributed models was consistently more reliable than any single model, and projection interval coverage was near target levels for the most plausible scenarios (e.g., 79% coverage for 95% projection interval). SMH projections were used operationally to guide planning and policy at different stages of the pandemic, illustrating the value of the hub approach for long-term scenario projections.

Objective: To create a commons for infectious disease (ID) epidemiology in which epidemiologists, public health officers, data producers, and software developers can not only share data and software, but receive assistance in improving their interoperability. Materials and Methods: We represented 586 datasets, 54 software, and 24 data formats in OWL 2 and then used logical queries to infer potentially interoperable combinations of software and datasets, as well as statistics about the FAIRness of the collection. We represented the objects in DATS 2.2 and a software metadata schema of our own design. We used these representations as the basis for the Content, Search, FAIR-o-meter, and Workflow pages that constitute the MIDAS Digital Commons. Results: Interoperability was limited by lack of standardization of input and output formats of software. When formats existed, they were human-readable specifications (22/24; 92%); only 3 formats (13%) had machine-readable specifications. Nevertheless, logical search of a triple store based on named data formats was able to identify scores of potentially interoperable combinations of software and datasets. Discussion: We improved the findability and availability of a sample of software and datasets and developed metrics for assessing interoperability. The barriers to interoperability included poor documentation of software input/output formats and little attention to standardization of most types of data in this field. Conclusion: Centralizing and formalizing the representation of digital objects within a commons promotes FAIRness, enables its measurement over time and the identification of potentially interoperable combinations of data and software.

Policymakers must make management decisions despite incomplete knowledge and conflicting model projections. Little guidance exists for the rapid, representative, and unbiased collection of policy-relevant scientific input from independent modeling teams. Integrating approaches from decision analysis, expert judgment, and model aggregation, we convened multiple modeling teams to evaluate COVID-19 reopening strategies for a mid-sized United States county early in the pandemic. Projections from seventeen distinct models were inconsistent in magnitude but highly consistent in ranking interventions. The 6-mo-ahead aggregate projections were well in line with observed outbreaks in mid-sized US counties. The aggregate results showed that up to half the population could be infected with full workplace reopening, while workplace restrictions reduced median cumulative infections by 82%. Rankings of interventions were consistent across public health objectives, but there was a strong trade-off between public health outcomes and duration of workplace closures, and no win-win intermediate reopening strategies were identified. Between-model variation was high; the aggregate results thus provide valuable risk quantification for decision making. This approach can be applied to the evaluation of management interventions in any setting where models are used to inform decision making. This case study demonstrated the utility of our approach and was one of several multimodel efforts that laid the groundwork for the COVID-19 Scenario Modeling Hub, which has provided multiple rounds of real-time scenario projections for situational awareness and decision making to the Centers for Disease Control and Prevention since December 2020.

SummaryBackgroundSARS-CoV-2 vaccination of persons aged 12 years and older has reduced disease burden in the United States. The COVID-19 Scenario Modeling Hub convened multiple modeling teams in September 2021 to project the impact of expanding vaccine administration to children 5-11 years old on anticipated COVID-19 burden and resilience against variant strains.MethodsNine modeling teams contributed state- and national-level projections for weekly counts of cases, hospitalizations, and deaths in the United States for the period September 12, 2021 to March 12, 2022. Four scenarios covered all combinations of: 1) presence vs. absence of vaccination of children ages 5-11 years starting on November 1, 2021; and 2) continued dominance of the Delta variant vs. emergence of a hypothetical more transmissible variant on November 15, 2021. Individual team projections were combined using linear pooling. The effect of childhood vaccination on overall and age-specific outcomes was estimated by meta-analysis approaches.FindingsAbsent a new variant, COVID-19 cases, hospitalizations, and deaths among all ages were projected to decrease nationally through mid-March 2022. Under a set of specific assumptions, models projected that vaccination of children 5-11 years old was associated with reductions in all-age cumulative cases (7.2%, mean incidence ratio [IR] 0.928, 95% confidence interval [CI] 0.880-0.977), hospitalizations (8.7%, mean IR 0.913, 95% CI 0.834-0.992), and deaths (9.2%, mean IR 0.908, 95% CI 0.797-1.020) compared with scenarios where children were not vaccinated. This projected effect of vaccinating children 5-11 years old increased in the presence of a more transmissible variant, assuming no change in vaccine effectiveness by variant. Larger relative reductions in cumulative cases, hospitalizations, and deaths were observed for children than for the entire U.S. population. Substantial state-level variation was projected in epidemic trajectories, vaccine benefits, and variant impacts.ConclusionsResults from this multi-model aggregation study suggest that, under a specific set of scenario assumptions, expanding vaccination to children 5-11 years old would provide measurable direct benefits to this age group and indirect benefits to the all-age U.S. population, including resilience to more transmissible variants.

In Spring 2021, the highly transmissible SARS-CoV-2 Delta variant began to cause increases in cases, hospitalizations, and deaths in parts of the United States. At the time, with slowed vaccination uptake, this novel variant was expected to increase the risk of pandemic resurgence in the US in summer and fall 2021. As part of the COVID-19 Scenario Modeling Hub, an ensemble of nine mechanistic models produced 6-month scenario projections for July–December 2021 for the United States. These projections estimated substantial resurgences of COVID-19 across the US resulting from the more transmissible Delta variant, projected to occur across most of the US, coinciding with school and business reopening. The scenarios revealed that reaching higher vaccine coverage in July–December 2021 reduced the size and duration of the projected resurgence substantially, with the expected impacts was largely concentrated in a subset of states with lower vaccination coverage. Despite accurate projection of COVID-19 surges occurring and timing, the magnitude was substantially underestimated 2021 by the models compared with the of the reported cases, hospitalizations, and deaths occurring during July–December, highlighting the continued challenges to predict the evolving COVID-19 pandemic. Vaccination uptake remains critical to limiting transmission and disease, particularly in states with lower vaccination coverage. Higher vaccination goals at the onset of the surge of the new variant were estimated to avert over 1.5 million cases and 21,000 deaths, although may have had even greater impacts, considering the underestimated resurgence magnitude from the model.

After a period of rapidly declining U.S. COVID-19 incidence during January-March 2021, increases occurred in several jurisdictions (1,2) despite the rapid rollout of a large-scale vaccination program. This increase coincided with the spread of more transmissible variants of SARS-CoV-2, the virus that causes COVID-19, including B.1.1.7 (1,3) and relaxation of COVID-19 prevention strategies such as those for businesses, large-scale gatherings, and educational activities. To provide long-term projections of potential trends in COVID-19 cases, hospitalizations, and deaths, COVID-19 Scenario Modeling Hub teams used a multiple-model approach comprising six models to assess the potential course of COVID-19 in the United States across four scenarios with different vaccination coverage rates and effectiveness estimates and strength and implementation of nonpharmaceutical interventions (NPIs) (public health policies, such as physical distancing and masking) over a 6-month period (April-September 2021) using data available through March 27, 2021 (4). Among the four scenarios, an accelerated decline in NPI adherence (which encapsulates NPI mandates and population behavior) was shown to undermine vaccination-related gains over the subsequent 2-3 months and, in combination with increased transmissibility of new variants, could lead to surges in cases, hospitalizations, and deaths. A sharp decline in cases was projected by July 2021, with a faster decline in the high-vaccination scenarios. High vaccination rates and compliance with public health prevention measures are essential to control the COVID-19 pandemic and to prevent surges in hospitalizations and deaths in the coming months.

Policymakers make decisions about COVID-19 management in the face of considerable uncertainty. We convened multiple modeling teams to evaluate reopening strategies for a mid-sized county in the United States, in a novel process designed to fully express scientific uncertainty while reducing linguistic uncertainty and cognitive biases. For the scenarios considered, the consensus from 17 distinct models was that a second outbreak will occur within 6 months of reopening, unless schools and non-essential workplaces remain closed. Up to half the population could be infected with full workplace reopening; non-essential business closures reduced median cumulative infections by 82%. Intermediate reopening interventions identified no win-win situations; there was a trade-off between public health outcomes and duration of workplace closures. Aggregate results captured twice the uncertainty of individual models, providing a more complete expression of risk for decision-making purposes.

BACKGROUND:We developed the Apollo Structured Vocabulary (Apollo-SV)-an OWL2 ontology of phenomena in infectious disease epidemiology and population biology-as part of a project whose goal is to increase the use of epidemic simulators in public health practice. Apollo-SV defines a terminology for use in simulator configuration. Apollo-SV is the product of an ontological analysis of the domain of infectious disease epidemiology, with particular attention to the inputs and outputs of nine simulators.RESULTS:Apollo-SV contains 802 classes for representing the inputs and outputs of simulators, of which approximately half are new and half are imported from existing ontologies. The most important Apollo-SV class for users of simulators is infectious disease scenario, which is a representation of an ecosystem at simulator time zero that has at least one infection process (a class) affecting at least one population (also a class). Other important classes represent ecosystem elements (e.g., households), ecosystem processes (e.g., infection acquisition and infectious disease), censuses of ecosystem elements (e.g., censuses of populations), and infectious disease control measures. In the larger project, which created an end-user application that can send the same infectious disease scenario to multiple simulators, Apollo-SV serves as the controlled terminology and strongly influences the design of the message syntax used to represent an infectious disease scenario. As we added simulators for different pathogens (e.g., malaria and dengue), the core classes of Apollo-SV have remained stable, suggesting that our conceptualization of the information required by simulators is sound. Despite adhering to the OBO Foundry principle of orthogonality, we could not reuse Infectious Disease Ontology classes as the basis for infectious disease scenarios. We thus defined new classes in Apollo-SV for host, pathogen, infection, infectious disease, colonization, and infection acquisition. Unlike IDO, our ontological analysis extended to existing mathematical models of key biological phenomena studied by infectious disease epidemiology and population biology.CONCLUSION:Our ontological analysis as expressed in Apollo-SV was instrumental in developing a simulator-independent representation of infectious disease scenarios that can be run on multiple epidemic simulators. Our experience suggests the importance of extending ontological analysis of a domain to include existing mathematical models of the phenomena studied by the domain. Apollo-SV is freely available at: http://purl.obolibrary.org/obo/apollo_sv.owl .

Introduction: Emergency Department (ED) records and over-the-counter (OTC) sales data are two of the most commonly used data sources for syndromic surveillance. Most current detection algorithms monitor these data sources separately, and either do not combine them, or combine them in an ad hoc fashion. This paper introduces a causal model that coherently combines the two data sources in order to perform outbreak detection. Objectives: This paper presents a Bayesian biosurveillance algorithm called PANDA that combines information from multiple data streams. We describe the model, along with an explication of assumptions and techniques used to make this approach scalable for real-time surveillance of a large population. Methods: We extend the causal Bayesian network model used in (1) to incorporate evidence from daily OTC sales data. We model, at the level of individual people, the actions that result in the purchase of OTC products, as well as admission to an ED. Results: The aim of this paper is to describe a detection model for monitoring both ED and OTC data. This paper provides preliminary support that despite the complexities of this model, the running time is tractable. Conclusion: This paper introduces a new Bayesian biosurveillance algorithm that models the interaction between ED and OTC data. It also provides preliminary results that are positive regarding the run time of the algorithm.

The Apollo Structured Vocabulary (Apollo-SV) is a Web Ontology Language 2 (OWL 2) representation of terms related to epidemic simulation. We are developing Apollo-SV by ontological analysis of the information used and created by epidemic simulators and the entities this information is about. A key finding of our analysis is that the input of an epidemic simulator is properly understood as (1) a representation of an ecosystem at simulator time zero, (2) information about infectious diseases of interest in the ecosystem, and (3) information about plans to control the diseases. This insight is reflected in the scope of Apollo-SV, which includes terms from the domains of both infectious disease epidemiology and population biology. We also found that some definitions in the Infectious Disease Ontology (IDO), including ‘infection’, ‘infection acquisition’, ‘infectious disease’, ‘pathogen’, and ‘host’, were not compatible with the meanings of the terms as used in epidemic simulation; thus, we created new definitions of these terms. Our analysis of epidemic simulators—which are mathematical models of phenomena studied by infectious disease epidemiology—afforded several advantages that likely explain why we discovered limitations of IDO. As a result, we recommend that development of biomedical ontologies intended for reuse consider the perspective of the overlapping biological science(s) involved. Apollo-SV is freely available at: http://purl.obolibrary.org/obo/apollo_sv.owl. Keywords—disease transmission models, epidemic simulators, biomedical ontology, infectious disease epidemiology

This paper describes the Apollo Web Services and Apollo-SV, its related ontology. The Apollo Web Services give an end-user application a single point of access to multiple epidemic simulators. An end user can specify an analytic problem-which we define as a configuration and a query of results-exactly once and submit it to multiple epidemic simulators. The end user represents the analytic problem using a standard syntax and vocabulary, not the native languages of the simulators. We have demonstrated the feasibility of this design by implementing a set of Apollo services that provide access to two epidemic simulators and two visualizer services.

Background: Previous studies have shown that diagnosis of Crohn's disease (CD) in childhood is associated with a different phenotype when compared to adults (higher risk for ileocolonic disease and fibrostenotic behavior), and may be associated with a more aggressive form of disease requiring more surgery.Those diagnosed at an older age have been reported to have an increased rate of isolated colonic disease and a milder course of disease requiring less surgery.Methods: A comprehensive medical chart review was done for 571 CD patients that were followed in a tertiary referral IBD clinic.Among the parameters that were recorded for each patient at specific time intervals were parameters of disease phenotype according to the Montreal Classification (A1 diagnosed ,16, n=88, A2 diagnosed 16-40, n=287, A3 diagnosed .40,n=77) as well as having surgery.Results: The study included 452 patients that had complete data in the charts.At 6 years from diagnosis and at last follow-up (median-11 years), A3 had a higher rate of isolated colonic disease than A1 but not in comparison to A2. Perianal involvement was significantly less common in A3 than A1 or A2.Complicated disease behavior (B2/B3) was similar for all three groups at both time frames.Nonetheless, at 6 years and last follow-up, IBD-related abdominal surgery rates were significantly lower for A1 vs. A2 and vs A3.Conclusions: While there are some disease location differences that emerge with increasing age of presentation (more isolated colonic disease and less perineal disease) disease behavior over time is similar regardless of age at diagnosis and surgeries were least likely in those diagnosed prior to age 16.Our study did not corroborate a more aggressive course for CD that presents in the pediatric age group.Outcomes at 6 years from diagnosis * p value is vs A3 cohort **p value is vs A1 cohort Outcomes at final follow from diagnosis * p value is vs A3 cohort **p value is vs A1 cohort Mo1341

Early, reliable detection of disease outbreaks is a critical problem today. This paper reports an investigation of the use of causal Bayesian networks to model spatio-temporal patterns of a non-contagious disease (respiratory anthrax infection) in a population of people. The number of parameters in such a network can become enormous, if not carefully managed. Also, inference needs to be performed in real time as population data stream in. We describe techniques we have applied to address both the modeling and inference challenges. A key contribution of this paper is the explication of assumptions and techniques that are sufficient to allow the scaling of Bayesian network modeling and inference to millions of nodes for real-time surveillance applications. The results reported here provide a proof-of-concept that Bayesian networks can serve as the foundation of a system that effectively performs Bayesian biosurveillance of disease outbreaks.

The Pittsburgh Center of Excellence in Public Health Informatics has developed a probabilistic, decision-theoretic system for disease surveillance and control for use in Allegheny County, PA and later in Tarrant County, TX. This paper describes the software components of the system and its knowledge bases. The paper uses influenza surveillance to illustrate how the software components transform data collected by the healthcare system into population level analyses and decision analyses of potential outbreak-control measures.

0.9606 (0.9551-0.9649) 0.9815 (0.978-0.9856) Syndrome 2 - Gastrointestinal 0.9823 (0.9797-0.9851) 0.9885 (0.9858-0.9919) Syndrome 3 - Constitutional 0.9293 (0.9207-0.9383) 0.9555 (0.9493-0.9619)