Co-Designing an Initiative to Increase Shared Access to Older Adults' Patient Portals: Stakeholder Engagement.

BACKGROUND: The patient portal is a widely available secure digital platform offered by care delivery organizations that enables patients to communicate electronically with clinicians and manage their care. Many organizations allow patients to authorize family members or friends-"care partners"-to share access to patient portal accounts, thus enabling care partners to receive their own identity credentials. Shared access facilitates trilateral information exchange among patients, clinicians, and care partners; however, uptake and awareness of this functionality are limited. OBJECTIVE: We partnered with 3 health care organizations to co-design an initiative that aimed to increase shared access registration and use and that can be implemented using existing patient portals. METHODS: In 2020, we undertook a rigorous selection process to identify 3 geographically diverse health care organizations that had engaged medical informatics teams and clinical champions within service delivery lines caring for older adults. We prioritized selecting organizations that serve racially and socioeconomically diverse populations and possess sophisticated reporting capabilities, a stable patient portal platform, a sufficient volume of older adult patients, and active patient and family advisory councils. Along with patients and care partners, clinicians, staff, and other stakeholders, the study team co-designed an initiative to increase the uptake of shared access guided by either an iterative, human-centered design process or rapid assessment procedures of stakeholders' inputs. RESULTS: Between February 2020 and April 2022, 73 stakeholder engagements were conducted with patients and care partners, clinicians and clinic staff, medical informatics teams, marketing and communications staff, and administrators, as well as with funders and thought leaders. We collected insights regarding (1) barriers to awareness, registration, and use of shared access; (2) features of consumer-facing educational materials to address identified barriers; (3) features of clinician- and staff-facing materials to address identified barriers; and (4) approaches to fit the initiative into current workflows. Using these inputs iteratively via a human-centered design process, we produced brochures and posters, co-designed organization-specific web pages detailing shared access registration processes, and developed clinician and staff talking points about shared access and staff tip sheets that outline shared access registration steps. Educational materials emphasized the slogan "People remember less than half of what their doctors say," which was selected from 9 candidate alternatives as resonating best with the full range of the initiative's stakeholders. The materials were accompanied by implementation toolkits specifying and reinforcing workflows involving both in-person and telehealth visits. CONCLUSIONS: Meaningful and authentic stakeholder engagement allowed our deliberate, iterative, and human-centered co-design aimed at increasing the use of shared access. Our initiative has been launched as a part of a 12-month demonstration that will include quantitative and qualitative analysis of registration and use of shared access. Educational materials are publicly available at Coalition for Care Partners.

Biomechanics Simulations Using Cubic Hermite Meshes with Extraordinary Nodes for Isogeometric Cardiac Modeling.

Cubic Hermite hexahedral finite element meshes have some well-known advantages over linear tetrahedral finite element meshes in biomechanical and anatomic modeling using isogeometric analysis. These include faster convergence rates as well as the ability to easily model rule-based anatomic features such as cardiac fiber directions. However, it is not possible to create closed complex objects with only regular nodes; these objects require the presence of extraordinary nodes (nodes with 3 or >= 5 adjacent elements in 2D) in the mesh. The presence of extraordinary nodes requires new constraints on the derivatives of adjacent elements to maintain continuity. We have developed a new method that uses an ensemble coordinate frame at the nodes and a local-to-global mapping to maintain continuity. In this paper, we make use of this mapping to create cubic Hermite models of the human ventricles and a four-chamber heart. We also extend the methods to the finite element equations to perform biomechanics simulations using these meshes. The new methods are validated using simple test models and applied to anatomically accurate ventricular meshes with valve annuli to simulate complete cardiac cycle simulations.

Structural contributions to fibrillatory rotors in a patient-derived computational model of the atria.

AIMS: The aim of this study was to investigate structural contributions to the maintenance of rotors in human atrial fibrillation (AF) and possible mechanisms of termination. METHODS AND RESULTS: A three-dimensional human biatrial finite element model based on patient-derived computed tomography and arrhythmia observed at electrophysiology study was used to study AF. With normal physiological electrical conductivity and effective refractory periods (ERPs), wave break failed to sustain reentrant activity or electrical rotors. With depressed excitability, decreased conduction anisotropy, and shorter ERP characteristic of AF, reentrant rotors were readily maintained. Rotors were transiently or permanently trapped by fibre discontinuities on the lateral wall of the right atrium near the tricuspid valve orifice and adjacent to the crista terminalis, both known sites of right atrial arrhythmias. Modelling inexcitable regions near the rotor tip to simulate fibrosis anchored the rotors, converting the arrhythmia to macro-reentry. Accordingly, increasing the spatial core of inexcitable tissue decreased the frequency of rotation, widened the excitable gap, and enabled an external wave to impinge on the rotor core and displace the source. CONCLUSION: These model findings highlight the importance of structural features in rotor dynamics and suggest that regions of fibrosis may anchor fibrillatory rotors. Increasing extent of fibrosis and scar may eventually convert fibrillation to excitable gap reentry. Such macro-reentry can then be eliminated by extending the obstacle or by external stimuli that penetrate the excitable gap.

Unmet palliative care service needs: a patient-centred metric.

OBJECTIVES: Financial pressures and competing demands for limited resources highlight the importance of defining the unmet need for specialty inpatient palliative care (PC), demonstrating the value of the service line and making decisions about staffing. One measure of access to specialty PC is penetration, the percentage of hospitalised adults receiving PC consultations. Although useful, additional means of quantifying programme performance are required for evaluating access by patients who would benefit. The study sought to define a simplified method of calculating unmet need for inpatient PC. METHODS: This retrospective observational study analysed electronic health records from six hospitals in one health system in Los Angeles County.Unmet need for PC was defined by the number of hospitalised patients with four or more chronic serious comorbidities without a PC consultation divided by a denominator of all patients with one or more chronic serious conditions (CSCs) without a PC during the hospitalisation. RESULTS: This calculation identified a subset of patients with four or more CSCs that accounts for 10.3% of the population of adults with one or more CSCs who did not receive PC services during a hospitalisation (unmet need). Monthly internal reporting of this metric led to significant PC programme expansion with an increase in average penetration for the six hospitals from 5.9% in 2017 to 11.2% in 2021. CONCLUSIONS: Health system leadership can benefit from quantifying the need for specialty PC among seriously ill inpatients. This anticipated measure of unmet need is a quality indicator that complements existing metrics.

Coronary Sinus Neuropeptide Y Levels and Adverse Outcomes in Patients With Stable Chronic Heart Failure.

Importance: Chronic heart failure (CHF) is associated with increased sympathetic drive and may increase expression of the cotransmitter neuropeptide Y (NPY) within sympathetic neurons. Objective: To determine whether myocardial NPY levels are associated with outcomes in patients with stable CHF. Design, Setting, and Participants: Prospective observational cohort study conducted at a single-center, tertiary care hospital. Stable patients with heart failure undergoing elective cardiac resynchronization therapy device implantation between 2013 and 2015. Main Outcomes and Measures: Chronic heart failure hospitalization, death, orthotopic heart transplantation, and ventricular assist device placement. Results: Coronary sinus (CS) blood samples were obtained during cardiac resynchronization therapy (CRT) device implantation in 105 patients (mean [SD] age 68 [12] years; 82 men [78%]; mean [SD] left ventricular ejection fraction [LVEF] 26% [7%]). Clinical, laboratory, and outcome data were collected prospectively. Stellate ganglia (SG) were collected from patients with CHF and control organ donors for molecular analysis. Mean (SD) CS NPY levels were 85.1 (31) pg/mL. On bivariate analyses, CS NPY levels were associated with estimated glomerular filtration rate (eGFR; rs = -0.36, P < .001); N-terminal-pro hormone brain natriuretic peptide (rs = 0.33; P = .004), and LV diastolic dimension (rs = -0.35; P < .001), but not age, LVEF, functional status, or CRT response. Adjusting for GFR, age, and LVEF, the hazard ratio for event-free (death, cardiac transplant, or left ventricular assist device) survival for CS NPY ≥ 130 pg/mL was 9.5 (95% CI, 2.92-30.5; P < .001). Immunohistochemistry demonstrated significantly reduced NPY protein (mean [SD], 13.7 [7.6] in the cardiomyopathy group vs 31.4 [3.7] in the control group; P < .001) in SG neurons from patients with CHF while quantitative polymerase chain reaction demonstrated similar mRNA levels compared with control individuals, suggesting increased release from SG neurons in patients with CHF. Conclusions and Relevance: The CS levels of NPY may be associated with outcomes in patients with stable CHF undergoing CRT irrespective of CRT response. Increased neuronal traffic and release may be the mechanism for elevated CS NPY levels in patients with CHF. Further studies are warranted to confirm these findings. Trial Registration: ClinicalTrials.gov identifier: NCT01949246.

An Employer Health Incentive Plan for Advance Care Planning and Goal-Aligned Care.

One strategy to promote workforce well-being has been health incentive plans, in which a company's insured employees are offered compensation for completing a particular health-related activity. In 2015, Providence Health & Services adopted an Advance Care Planning (ACP) activity as a 2015-2016 health incentive option. More than 51,000 employees and their insured relatives chose the ACP incentive option. More than 80% rated the experience as helpful or very helpful. A high proportion (95%) of employees responded that they had someone they trusted who could make medical care decisions for them, yet only 23% had completed an advance directive, and even fewer (11%) had shared the document with their health care provider. The most common reason given for not completing an advance directive was that health care providers had never asked about it. These findings suggest that an insured employee incentive plan can encourage ACP consistent with the health care organizations' values and strategic priorities.

Human immunodeficiency virus reverse transcriptase and protease sequence database.

The HIV reverse transcriptase and protease sequence database is an on-line relational database that catalogues evolutionary and drug-related sequence variation in the human immunodeficiency virus (HIV) reverse transcriptase (RT) and protease enzymes, the molecular targets of antiretroviral therapy (http://hivdb.stanford.edu). The database contains a compilation of nearly all published HIV RT and protease sequences, including submissions to GenBank, sequences published in journal articles and sequences of HIV isolates from persons participating in clinical trials. Sequences are linked to data about the source of the sequence, the antiretroviral drug treatment history of the person from whom the sequence was obtained and the results of in vitro drug susceptibility testing. Sequence data on two new molecular targets of HIV drug therapy--gp41 (cell fusion) and integrase--will be added to the database in 2003.

Panel of prototypical infectious molecular HIV-1 clones containing multiple nucleoside reverse transcriptase inhibitor resistance mutations.

We have created a panel of recombinant HIV-1 infectious clones containing common patterns of reverse transcriptase (RT) mutations responsible for resistance to each of the currently available nucleoside reverse transcriptase inhibitors (NRTI), and we have submitted the panel to the National Institutes of Health AIDS Research and Reference Reagent Programme. Testing the activity of new antiretroviral compounds against this panel of drug-resistant clones will determine their relative activity against many clinically relevant NRTI-resistant viruses.

High-order finite element methods for cardiac monodomain simulations.

Computational modeling of tissue-scale cardiac electrophysiology requires numerically converged solutions to avoid spurious artifacts. The steep gradients inherent to cardiac action potential propagation necessitate fine spatial scales and therefore a substantial computational burden. The use of high-order interpolation methods has previously been proposed for these simulations due to their theoretical convergence advantage. In this study, we compare the convergence behavior of linear Lagrange, cubic Hermite, and the newly proposed cubic Hermite-style serendipity interpolation methods for finite element simulations of the cardiac monodomain equation. The high-order methods reach converged solutions with fewer degrees of freedom and longer element edge lengths than traditional linear elements. Additionally, we propose a dimensionless number, the cell Thiele modulus, as a more useful metric for determining solution convergence than element size alone. Finally, we use the cell Thiele modulus to examine convergence criteria for obtaining clinically useful activation patterns for applications such as patient-specific modeling where the total activation time is known a priori.

Extended spectrum of HIV-1 reverse transcriptase mutations in patients receiving multiple nucleoside analog inhibitors.

OBJECTIVE: To characterize reverse transcriptase (RT) mutations by their association with extent of nucleoside RT inhibitor (NRTI) therapy. To identify mutational clusters in RT sequences from persons receiving multiple NRTI. DESIGN: A total of 1210 RT sequences from persons with known antiretroviral therapy were analyzed: 641 new sequences were performed at Stanford University Hospital; 569 were previously published. METHODS: Chi-square tests and logistic regression were done to identify associations between mutations and NRTI therapy. Correlation studies were done to identify mutational clusters. The Benjamini-Hochberg procedure was used to correct for multiple comparisons. RESULTS: Mutations at 26 positions were significantly associated with NRTI including 17 known resistance mutations (positions 41, 44, 62, 65, 67, 69, 70, 74, 75, 77, 116, 118, 151, 184, 210, 215, 219) and nine previously unreported mutations (positions 20, 39, 43, 203, 208, 218, 221, 223, 228). The nine new mutations correlated linearly with number of NRTI; 777 out of 817 (95%) instances occurred with known drug resistance mutations. Positions 203, 208, 218, 221, 223, and 228 were conserved in untreated persons; positions 20, 39, and 43 were polymorphic. Most NRTI-associated mutations clustered into three groups: (i) 62, 65, 75, 77, 115, 116, 151; (ii) 41, 43, 44, 118, 208, 210, 215, 223; (iii) 67, 69, 70, 218, 219, 228. CONCLUSIONS: Mutations at nine previously unreported positions are associated with NRTI therapy. These mutations are probably accessory because they occur almost exclusively with known drug resistance mutations. Most NRTI mutations group into one of three clusters, although several (e.g., M184V) occur in multiple mutational contexts.

Protease and reverse transcriptase mutation patterns in HIV type 1 isolates from heavily treated persons: comparison of isolates from Northern California with isolates from other regions.

We compared HIV-1 subtype B reverse transcriptase (RT) and protease mutation patterns in isolates from heavily treated persons in Northern California with those from persons described in the published literature predominantly from other parts of the United States and Europe. There were few differences in the prevalence of single, double, and triple mutations between the two sets of sequences. More complex patterns of mutations could be characterized by clustering the sequences into eight groups of RT sequences and nine groups of protease sequences according to the presence of known drug-resistance mutations. This clustering accounted for 63% of the variation at RT inhibitor-resistance positions and 68% of the variation at protease inhibitor-resistance positions. The majority of clusters contained Northern California and literature sequences in similar proportions.

Identification of Ugandan HIV type 1 variants with unique patterns of recombination in pol involving subtypes A and D.

Most HIV-1 infections in Uganda are caused by subtypes A and D. The prevalence of recombination and the sites of specific breakpoints between these subtypes have not been reported. HIV-1 pol sequences encoding protease (amino acids 1-99) and reverse transcriptase (amino acids 1-324) from 102 pregnant Ugandan women were analyzed by the Recombinant Identification Program, SimPlot, and examination of phylogenetically informative sites to identify sites of recombination between sequence segments belonging to different subtypes. Thirteen percent (13 of 102) of the pol sequences contained strong evidence of recombination between subtypes A and D. At least nine different patterns of recombination were observed. Five women infected with a recombinant virus transmitted the recombinant virus perinatally. In this population-based study, intersubtype recombinants were common. The large number of different types of pol recombinants identified suggests that recombination occurs readily in the pol region. Perinatal transmission of the recombinant viruses demonstrates their evolutionary stability.

A three-dimensional finite element model of human atrial anatomy: new methods for cubic Hermite meshes with extraordinary vertices.

High-order cubic Hermite finite elements have been valuable in modeling cardiac geometry, fiber orientations, biomechanics, and electrophysiology, but their use in solving three-dimensional problems has been limited to ventricular models with simple topologies. Here, we utilized a subdivision surface scheme and derived a generalization of the "local-to-global" derivative mapping scheme of cubic Hermite finite elements to construct bicubic and tricubic Hermite models of the human atria with extraordinary vertices from computed tomography images of a patient with atrial fibrillation. To an accuracy of 0.6 mm, we were able to capture the left atrial geometry with only 142 bicubic Hermite finite elements, and the right atrial geometry with only 90. The left and right atrial bicubic Hermite meshes were G1 continuous everywhere except in the one-neighborhood of extraordinary vertices, where the mean dot products of normals at adjacent elements were 0.928 and 0.925. We also constructed two biatrial tricubic Hermite models and defined fiber orientation fields in agreement with diagrammatic data from the literature using only 42 angle parameters. The meshes all have good quality metrics, uniform element sizes, and elements with aspect ratios near unity, and are shared with the public. These new methods will allow for more compact and efficient patient-specific models of human atrial and whole heart physiology.

An atlas-based geometry pipeline for cardiac Hermite model construction and diffusion tensor reorientation.

Here we present a novel atlas-based geometry pipeline for constructing three-dimensional cubic Hermite finite element meshes of the whole human heart from tomographic patient image data. To build the cardiac atlas, two superior atria, two inferior ventricles as well as the aorta and the pulmonary trunk are first segmented, and epicardial and endocardial boundary surfaces are extracted and smoothed. Critical points and skeletons (or central-line paths) are identified, following the cardiac topology. The surface model and the path tree are used to construct a hexahedral control mesh via a skeleton-based sweeping method. Derivative parameters are computed from the control mesh, defining cubic Hermite finite elements. The thickness of the atria and the ventricles is obtained using segmented epicardial boundaries or via offsetting from the endocardial surfaces in regions where the image resolution is insufficient. We also develop a robust optical flow approach to deform the constructed atlas and align it with the image from a second patient. This registration method is fully-automatic, and avoids manual operations required by segmentation and path extraction. Moreover, we demonstrate that this method can also be used to deformably map diffusion tensor MRI data with patient geometries to include fiber and sheet orientations in the finite element model.

Nausea and other nonpain symptoms in long-term care.

There is a need to improve the quality of end-of-life care in nursing homes by improving the timely assessment and management of various sources of suffering. Much of the research/discussion in this area has focused on the assessment and treatment of pain. This article reviews the frequency and management of nonpain symptoms in the long-term care setting, particularly focusing on patients at the end of life. Although the long-term care setting presents challenges to effective management, an approach for addressing these challenges is discussed and applied to 3 commonly encountered nonpain symptoms.

Patient-specific modeling of dyssynchronous heart failure: a case study.

The development and clinical use of patient-specific models of the heart is now a feasible goal. Models have the potential to aid in diagnosis and support decision-making in clinical cardiology. Several groups are now working on developing multi-scale models of the heart for understanding therapeutic mechanisms and better predicting clinical outcomes of interventions such as cardiac resynchronization therapy. Here we describe the methodology for generating a patient-specific model of the failing heart with a myocardial infarct and left ventricular bundle branch block. We discuss some of the remaining challenges in developing reliable patient-specific models of cardiac electromechanical activity, and identify some of the main areas for focusing future research efforts. Key challenges include: efficiently generating accurate patient-specific geometric meshes and mapping regional myofiber architecture to them; modeling electrical activation patterns based on cellular alterations in human heart failure, and estimating regional tissue conductivities based on clinically available electrocardiographic recordings; estimating unloaded ventricular reference geometry and material properties for biomechanical simulations; and parameterizing systemic models of circulatory dynamics from available hemodynamic measurements.

The Genetic Basis of HIV-1 Resistance to Reverse Transcriptase and Protease Inhibitors.

HIV-1 drug resistance is caused by mutations in the reverse transcriptase (RT) and protease enzymes, the molecular targets of antiretroviral therapy. At the beginning of the year 2000, two expert panels recommended that HIV-1 RT and protease susceptibility testing be used to help select antiretroviral drugs for HIV-1-infected patients. Genotypic assays have been developed to detect HIV-1 mutations known to confer antiretroviral drug resistance. Genotypic assays using dideoxynucleoside sequencing provide extensive insight into the presence of drug-resistant variants in the population of viruses within an individual. However, the interpretation of these assays in clinical settings is formidable because of the large numbers of drug resistance mutations and because these mutations interact with one another and emerge in complex patterns. In addition, cross-resistance between antiretroviral drugs is greater than that anticipated from initial in vitro studies. This review summarises the published data linking HIV-1 RT and protease mutations to in vitro and clinical resistance to the currently available nucleoside RT inhibitors, non-nucleoside RT inhibitors, and protease inhibitors.

Synonymous-non-synonymous mutation rates between sequences containing ambiguous nucleotides (Syn-SCAN).

SUMMARY: Direct PCR sequencing on genetic material containing allelic mixtures results in sequences containing ambiguous nucleotides. Because codons exhibiting allelic mixtures present evidence of evolutionary pressure, it is important to include this information in the assessment of codon synonymy. We developed a program, 'Synonymous-Nonsynonymous Mutation Rates between Sequences Containing Ambiguous Nucleotides' (Syn-SCAN), that calculates synonymous and non-synonymous substitution rates using a model that includes allelic mixtures. AVAILABILITY: Syn-SCAN is implemented on the web and can be downloaded from http://hivdb.stanford.edu.

Colinearity of reverse transcriptase inhibitor resistance mutations detected by population-based sequencing.

High-level resistance to multiple drugs is often detected by directly sequencing uncloned polymerase chain reaction products (population-based sequencing). It is not known, however, if this method of identifying mutations gives an accurate picture of individual viral genomes. To determine how often multidrug-resistant isolates consist of clones containing every mutation present in the population-based sequence, a mean of 2.8 molecular clones was sequenced from the plasma of 25 heavily treated persons whose population-based sequence contained multiple reverse transcriptase (RT) inhibitor resistance mutations (71 clones). The 25 population-based sequences contained a mean of 5.7 nucleoside reverse transcriptase inhibitor (NRTI) resistance mutations and 1.2 nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance mutations. The 71 clones contained a mean of 5.3 NRTI resistance mutations and 1.0 NNRTI resistance mutations. Sequences of clones closely resembled the population-based sequence: 36 (51%) clones had each of the RT inhibitor mutations present in the population-based sequence, 25 (35%) had all but 1 RT inhibitor mutation, 4 (6%) had all but 2 RT inhibitor mutations, 3 (4%) had all but 3 RT inhibitor mutations, and 3 (4%) had all but 4 RT inhibitor mutations. Phenotypic testing of 29 clones showed that most clones were resistant to nearly all NRTIs and that those with NNRTI resistance mutations were also resistant to multiple NNRTIs. These data show that in heavily treated persons, most RT inhibitor resistance mutations are present in the same viral genomes (colinear) and that multidrug resistance often occurs within individual clones as well as within virus populations.