Implementing an osteoarthritis management program to deliver guideline-driven care for knee and hip osteoarthritis in a U.S. academic health system.

Objective: Assess implementation feasibility and outcomes for an Osteoarthritis Management Program (OAMP) at an academic center. Design: This open study assessed an OAMP designed to deliver care in 1-5 individual or group visits across ≤12 months. Eligibility included adults with knee or hip osteoarthritis with ≥1 visit from 7/1/2017-1/15/2021. A multidisciplinary care team provided: education on osteoarthritis, self-management, exercise, weight loss; pharmacologic management; assessments of mood, sleep, quality of life, and diet. Clinic utilization and growth are reported through 2022. Patient outcomes of body mass index (BMI), pain, and function were analyzed using multivariable general linear models. OAMP outcomes were feasibility and sustainability. Results: Most patients were locally referred by primary care. 953 patients attended 2531 visits (average visits 2.16, treatment duration 187.9 days). Most were female (72.6%), older (62.1), white (91.1%), and had medical insurance (95.4%). Obesity was prevalent (84.7% BMI ≥30, average BMI 40.9), mean Charlson Comorbidity Index was 1.89, and functional testing was below average. Longitudinal modeling revealed statistically but not clinically significant pain reduction (4.4-3.9 on 0-10 scale, p â€‹= â€‹0.002). BMI did not significantly change (p â€‹= â€‹0.87). Higher baseline pain and BMI correlated with greater reductions in each posttreatment. Uninsured patients had shorter treatment duration. Increasing clinic hours (4-24 â€‹h weekly) and serving 953 patients over four years demonstrated OAMP sustainability. Conclusions: OAMP implementation was feasible and sustainable. Patients with high baseline pain and BMI were more likely to improve. Noninsurance was a barrier. These results contribute to understanding OAMP outcomes in U.S. healthcare.

Prevalence of Antibiotic Allergy at a Spinal Cord Injury Center.

Background: Infectious diseases are the most common reason for rehospitalization in patients with spinal cord injury (SCI). Persons with SCI are at high risk for antibiotic over-use and hospital-acquired infection due to chronic bacteriuria, frequent health care exposure, implanted medical devices, and other factors. We aimed to record the percentage of subjects from the local SCI registry with an antibiotic allergy, the most common antibiotic classes responsible for the allergy, and allergic reactions. Methods: We conducted a retrospective study at the James A. Haley Veterans' Hospital in Tampa, Florida, of patients in the SCI registry between October 1, 2015, and September 30, 2017. We collected patient demographics and SCI descriptors. The outcomes included antibiotic allergy and adverse drug reactions. Results: Of 1866 patients, 1659 met inclusion criteria; 29.8% of the subjects had a recorded allergy to antibiotics. Penicillin (13.1%), sulfa drugs (9.6%), and fluoroquinolone (4.5%) were the most common allergens. However, only 11.9% of patients with a penicillin allergy had severe reactions. Conclusions: Almost 30% of patients with SCI had a recorded allergy to an antibiotic. There are opportunities to examine whether approaches to confirm true reactions, such as skin testing, would help mitigate unnecessary avoidance of certain antibiotic classes due to mild adverse effects, rather than a true allergy, in the SCI population. Differentiating true allergy is the only clear way to deter unnecessary avoidance of first-line therapies for antibiotic treatment and avoid promotion of antibiotic resistance.

Prevalence and Predictors of Lower Limb Amputation in the Spinal Cord Injury Population.

Background: Despite limited data demonstrating altered hemodynamics in the lower extremities (LEs) among the population with spinal cord injury (SCI) and increased frequency of peripheral arterial disease (PAD), epidemiologic data are limited for amputations, a potential consequence. This study investigates the association of amputation due to vascular complications as a secondary outcome measure within the SCI population. Methods: A retrospective cohort study was performed within a veteran population with SCI at a US Department of Veteran Affairs hospital to determine the prevalence of limb loss. We hypothesized that premorbid SCI increased the likelihood of LE amputation. Results: Of 1055 charts reviewed, 91 (8.7%) patients had an amputation, 70 (76.1%) had a dysvascular etiology. Transfemoral amputations were the most common level (n = 53) of amputation. Our results showed a positive correlation between the completeness of injury and the prevalence of amputation. Conclusion: There is an increased frequency of amputation among the veteran population with SCI compared with that of the general US population. Amputations frequently occur at more proximal levels with motor complete injuries. Studies using a larger population and multiple centers are needed to confirm this alarming trend.

A Robotic Hand Device Safety Study for People With Cervical Spinal Cord Injury.

This study of the FES Hand Glove 200 device suggests possible efficacy in enhancing range of motion of various wrist and finger joints.

Climate and Developmental Plasticity: Interannual Variability in Grapevine Leaf Morphology.

The shapes of leaves are dynamic, changing over evolutionary time between species, within a single plant producing different shaped leaves at successive nodes, during the development of a single leaf as it allometrically expands, and in response to the environment. Notably, strong correlations between the dissection and size of leaves with temperature and precipitation exist in both the paleorecord and extant populations. Yet, a morphometric model integrating evolutionary, developmental, and environmental effects on leaf shape is lacking. Here, we continue a morphometric analysis of >5,500 leaves representing 270 grapevines of multiple Vitis species between two growing seasons. Leaves are paired one-to-one and vine-to-vine accounting for developmental context, between growing seasons. Linear discriminant analysis reveals shape features that specifically define growing season, regardless of species or developmental context. The shape feature, a more pronounced distal sinus, is associated with the colder, drier growing season, consistent with patterns observed in the paleorecord. We discuss the implications of such plasticity in a long-lived woody perennial, such as grapevine (Vitis spp.), with respect to the evolution and functionality of plant morphology and changes in climate.

The Open Physiology workflow: modeling processes over physiology circuitboards of interoperable tissue units.

A key challenge for the physiology modeling community is to enable the searching, objective comparison and, ultimately, re-use of models and associated data that are interoperable in terms of their physiological meaning. In this work, we outline the development of a workflow to modularize the simulation of tissue-level processes in physiology. In particular, we show how, via this approach, we can systematically extract, parcellate and annotate tissue histology data to represent component units of tissue function. These functional units are semantically interoperable, in terms of their physiological meaning. In particular, they are interoperable with respect to [i] each other and with respect to [ii] a circuitboard representation of long-range advective routes of fluid flow over which to model long-range molecular exchange between these units. We exemplify this approach through the combination of models for physiology-based pharmacokinetics and pharmacodynamics to quantitatively depict biological mechanisms across multiple scales. Links to the data, models and software components that constitute this workflow are found at http://open-physiology.org/.

Distributed model construction with virtual parts.

Here three models for a simple genetic device are constructed using modular mathematical models. The models are stored in an online system (the Physiome Model Repository) with distributed source and access control, demonstrating a collaborative method for creating mathematical models from reusable components.

FieldML, a proposed open standard for the Physiome project for mathematical model representation.

The FieldML project has made significant progress towards the goal of addressing the need to have open standards and open source software for representing finite element method (FEM) models and, more generally, multivariate field models, such as many of the models that are core to the euHeart project and the Physiome project. FieldML version 0.5 is the most recently released format from the FieldML project. It is an XML format that already has sufficient capability to represent the majority of euHeart's explicit models such as the anatomical FEM models and simulation solution fields. The details of FieldML version 0.5 are presented, as well as its limitations and some discussion of the progress being made to address these limitations.

Space-Time Localization and Registration on the Beating Heart.

This paper presents a framework for localizing a miniature epicardial crawling robot, HeartLander, on the beating heart using only 6-degree-of-freedom position measurements from an electromagnetic position tracker and a dynamic surface model of the heart. Using only this information, motion and observation models of the system are developed such that a particle filter can accurately estimate not only the location of the robot on the surface of the heart, but also the pose of the heart in the world coordinate frame as well as the current physiological phase of the heart. The presented framework is then demonstrated in simulation on a dynamic 3-D model of the human heart and a robot motion model which accurately mimics the behavior of the HeartLander robot.

Towards localizing on the surface of the beating heart.

This paper presents preliminary work toward localizing on a surface which undergoes periodic deformation, as an aspect of research on HeartLander, a miniature epicardial crawling robot. Using only position measurements from the robot, the aim of this work is to use the nonuniform movements of the heart as features to aid in localization. Using a particle filter, with motion and observation models which accurately model the robotic system, registration and localization parameters can be quickly and accurately identified. The presented framework is demonstrated in simulation on dynamic 2-D models which approximate the deformation of the surface of the heart.

Model annotation for synthetic biology: automating model to nucleotide sequence conversion.

MOTIVATION: The need for the automated computational design of genetic circuits is becoming increasingly apparent with the advent of ever more complex and ambitious synthetic biology projects. Currently, most circuits are designed through the assembly of models of individual parts such as promoters, ribosome binding sites and coding sequences. These low level models are combined to produce a dynamic model of a larger device that exhibits a desired behaviour. The larger model then acts as a blueprint for physical implementation at the DNA level. However, the conversion of models of complex genetic circuits into DNA sequences is a non-trivial undertaking due to the complexity of mapping the model parts to their physical manifestation. Automating this process is further hampered by the lack of computationally tractable information in most models. RESULTS: We describe a method for automatically generating DNA sequences from dynamic models implemented in CellML and Systems Biology Markup Language (SBML). We also identify the metadata needed to annotate models to facilitate automated conversion, and propose and demonstrate a method for the markup of these models using RDF. Our algorithm has been implemented in a software tool called MoSeC. AVAILABILITY: The software is available from the authors' web site http://research.ncl.ac.uk/synthetic_biology/downloads.html.

The Physiome Model Repository 2.

MOTIVATION: The Physiome Model Repository 2 (PMR2) software was created as part of the IUPS Physiome Project (Hunter and Borg, 2003), and today it serves as the foundation for the CellML model repository. Key advantages brought to the end user by PMR2 include: facilities for model exchange, enhanced collaboration and a detailed change history for each model. AVAILABILITY: PMR2 is available under an open source license at http://www.cellml.org/tools/pmr/; a fully functional instance of this software can be accessed at http://models.physiomeproject.org/.

Revision history aware repositories of computational models of biological systems.

BACKGROUND: Building repositories of computational models of biological systems ensures that published models are available for both education and further research, and can provide a source of smaller, previously verified models to integrate into a larger model. One problem with earlier repositories has been the limitations in facilities to record the revision history of models. Often, these facilities are limited to a linear series of versions which were deposited in the repository. This is problematic for several reasons. Firstly, there are many instances in the history of biological systems modelling where an 'ancestral' model is modified by different groups to create many different models. With a linear series of versions, if the changes made to one model are merged into another model, the merge appears as a single item in the history. This hides useful revision history information, and also makes further merges much more difficult, as there is no record of which changes have or have not already been merged. In addition, a long series of individual changes made outside of the repository are also all merged into a single revision when they are put back into the repository, making it difficult to separate out individual changes. Furthermore, many earlier repositories only retain the revision history of individual files, rather than of a group of files. This is an important limitation to overcome, because some types of models, such as CellML 1.1 models, can be developed as a collection of modules, each in a separate file. The need for revision history is widely recognised for computer software, and a lot of work has gone into developing version control systems and distributed version control systems (DVCSs) for tracking the revision history. However, to date, there has been no published research on how DVCSs can be applied to repositories of computational models of biological systems. RESULTS: We have extended the Physiome Model Repository software to be fully revision history aware, by building it on top of Mercurial, an existing DVCS. We have demonstrated the utility of this approach, when used in conjunction with the model composition facilities in CellML, to build and understand more complex models. We have also demonstrated the ability of the repository software to present version history to casual users over the web, and to highlight specific versions which are likely to be useful to users. CONCLUSIONS: Providing facilities for maintaining and using revision history information is an important part of building a useful repository of computational models, as this information is useful both for understanding the source of and justification for parts of a model, and to facilitate automated processes such as merges. The availability of fully revision history aware repositories, and associated tools, will therefore be of significant benefit to the community.

Sharing and reusing cardiovascular anatomical models over the Web: a step towards the implementation of the virtual physiological human project.

Sharing and reusing anatomical models over the Web offers a significant opportunity to progress the investigation of cardiovascular diseases. However, the current sharing methodology suffers from the limitations of static model delivery (i.e. embedding static links to the models within Web pages) and of a disaggregated view of the model metadata produced by publications and cardiac simulations in isolation. In the context of euHeart--a research project targeting the description and representation of cardiovascular models for disease diagnosis and treatment purposes--we aim to overcome the above limitations with the introduction of euHeartDB, a Web-enabled database for anatomical models of the heart. The database implements a dynamic sharing methodology by managing data access and by tracing all applications. In addition to this, euHeartDB establishes a knowledge link with the physiome model repository by linking geometries to CellML models embedded in the simulation of cardiac behaviour. Furthermore, euHeartDB uses the exFormat--a preliminary version of the interoperable FieldML data format--to effectively promote reuse of anatomical models, and currently incorporates Continuum Mechanics, Image Analysis, Signal Processing and System Identification Graphical User Interface (CMGUI), a rendering engine, to provide three-dimensional graphical views of the models populating the database. Currently, euHeartDB stores 11 cardiac geometries developed within the euHeart project consortium.

CellML metadata standards, associated tools and repositories.

The development of standards for encoding mathematical models is an important component of model building and model sharing among scientists interested in understanding multi-scale physiological processes. CellML provides such a standard, particularly for models based on biophysical mechanisms, and a substantial number of models are now available in the CellML Model Repository. However, there is an urgent need to extend the current CellML metadata standard to provide biological and biophysical annotation of the models in order to facilitate model sharing, automated model reduction and connection to biological databases. This paper gives a broad overview of a number of new developments on CellML metadata and provides links to further methodological details available from the CellML website.