The State-of-the-Art of Patient Portals: Adapting to External Factors, Addressing Barriers, and Innovating.

BACKGROUND AND OBJECTIVE: Recent external factors-the 21st Century Cures Act and the coronavirus disease 2019 (COVID-19) pandemic-have stimulated major changes in the patient portal landscape. The objective of this state-of-the-art review is to describe recent developments in the patient portal literature and to identify recommendations and future directions for the design, implementation, and evaluation of portals. METHODS: To focus this review on salient contemporary issues, we elected to center it on four topics: (1) 21st Century Cures Act's impact on patient portals (e.g., Open Notes); (2) COVID-19's pandemic impact on portals; (3) proxy access to portals; and (4) disparities in portal adoption and use. We conducted targeted PubMed searches to identify recent empirical studies addressing these topics, used a two-part screening process to determine relevance, and conducted thematic analyses. RESULTS: Our search identified 174 unique papers, 74 were relevant empirical studies and included in this review. Among these papers, we identified 10 themes within our four a priori topics, including preparing for and understanding the consequences of increased patient access to their electronic health information (Cures Act); developing, deploying, and evaluating new virtual care processes (COVID-19); understanding current barriers to formal proxy use (proxy access); and addressing disparities in portal adoption and use (disparities). CONCLUSION: Our results suggest that the recent trends toward understanding the implications of immediate access to most test results, exploring ways to close gaps in portal adoption and use among different sub-populations, and finding ways to leverage portals to improve health and health care are the next steps in the maturation of patient portals and are key areas that require more research. It is important that health care organizations share their innovative portal efforts, so that successful measures can be tested in other contexts, and progress can continue.

Empowering patients to address diabetes care gaps: formative usability testing of a novel patient portal intervention.

Objective: The aim of this study was to design and assess the formative usability of a novel patient portal intervention designed to empower patients with diabetes to initiate orders for diabetes-related monitoring and preventive services. Materials and Methods: We used a user-centered Design Sprint methodology to create our intervention prototype and assess its usability with 3 rounds of iterative testing. Participants (5/round) were presented with the prototype and asked to perform common, standardized tasks using think-aloud procedures. A facilitator rated task performance using a scale: (1) completed with ease, (2) completed with difficulty, and (3) failed. Participants completed the System Usability Scale (SUS) scored 0-worst to 100-best. All testing occurred remotely via Zoom. Results: We identified 3 main categories of usability issues: distrust about the automated system, content concerns, and layout difficulties. Changes included improving clarity about the ordering process and simplifying language; however, design constraints inherent to the electronic health record system limited our ability to respond to all usability issues (eg, could not modify fixed elements in layout). Percent of tasks completed with ease across each round were 67%, 60%, and 80%, respectively. Average SUS scores were 87, 74, and 93, respectively. Across rounds, participants found the intervention valuable and appreciated the concept of patient-initiated ordering. Conclusions: Through iterative user-centered design and testing, we improved the usability of the patient portal intervention. A tool that empowers patients to initiate orders for disease-specific services as part of their existing patient portal account has potential to enhance the completion of recommended health services and improve clinical outcomes.

Radio Frequency Heating of Washable Conductive Textiles for Bacteria and Virus Inactivation.

The ongoing COVID-19 pandemic has increased the use of single-use medical fabrics such as surgical masks, respirators, and other personal protective equipment (PPE), which have faced worldwide supply chain shortages. Reusable PPE is desirable in light of such shortages; however, the use of reusable PPE is largely restricted by the difficulty of rapid sterilization. In this work, we demonstrate successful bacterial and viral inactivation through remote and rapid radio frequency (RF) heating of conductive textiles. The RF heating behavior of conductive polymer-coated fabrics was measured for several different fabrics and coating compositions. Next, to determine the robustness and repeatability of this heating response, we investigated the textile's RF heating response after multiple detergent washes. Finally, we show a rapid reduction of bacteria and virus by RF heating our conductive fabric. 99.9% of methicillin-resistant Staphylococcus aureus (MRSA) was removed from our conductive fabrics after only 10 min of RF heating; human cytomegalovirus (HCMV) was completely sterilized after 5 min of RF heating. These results demonstrate that RF heating conductive polymer-coated fabrics offer new opportunities for applications of conductive textiles in the medical and/or electronic fields.

Manipulating the solution environment to control the surface roughness of elastin-based polymer coatings.

Elastin-like polypeptides (ELP) have been used as a genetically-engineered, biocompatible substitute for elastin. Cell culture coatings prepared using ELP conjugated to low molecular weight polyethyleneimine (PEI) entices cells to form three-dimensional cellular aggregates that mimic their in vivo counterparts. This study seeks to control the deposition of the ELP and ELP-PEI molecules to control the roughness of the final coatings. The two polymers were coated onto three different substrates (glass, polystyrene, tissue-culture polystyrene) and the solution environment was altered by changing the polymer concentration (0.5, 1.0, 1.5 mg/mL) and/or salt concentration (None, 0.2 M phosphate buffered saline) for a total of 36 conditions. Atomic force microscopy (AFM) was used to measure the average roughness (Ra) of the samples and found that ELP coated samples had a higher Ra than their ELP-PEI counterparts. The coatings were tested for stability by performing cell culture media changes every three days for 11 days. AFM showed that the average roughness of the tested samples increased with each media change. To address this, the surfaces were crosslinked using hexamethyl diisocyanate, which minimized the change in surface roughness even when subjected to an intense sonication process. This study provides parameters to achieve elastin-based coatings with controlled roughness that can be used to support stable, long-term in vitro cell culture.

Machine learning to determine optimal conditions for controlling the size of elastin-based particles.

This paper evaluates the aggregation behavior of a potential drug and gene delivery system that combines branched polyethyleneimine (PEI), a positively-charged polyelectrolyte, and elastin-like polypeptide (ELP), a recombinant polymer that exhibits lower critical solution temperature (LCST). The LCST behavior of ELP has been extensively studied, but there are no quantitative ways to control the size of aggregates formed after the phase transition. The aggregate size cannot be maintained when the temperature is lowered below the LCST, unless the system exhibits hysteresis and forms irreversible aggregates. This study shows that conjugation of ELP with PEI preserves the aggregation behavior that occurs above the LCST and achieves precise aggregate radii when the solution conditions of pH (3, 7, 10), polymer concentration (0.1, 0.15, 0.3 mg/mL), and salt concentration (none, 0.2, 1 M) are carefully controlled. K-means cluster analyses showed that salt concentration was the most critical factor controlling the hydrodynamic radius and LCST. Conjugating ELP to PEI allowed crosslinking the aggregates and achieved stable particles that maintained their size below LCST, even after removal of the harsh (high salt or pH) conditions used to create them. Taken together, the ability to control aggregate sizes and use of crosslinking to maintain stability holds excellent potential for use in biological delivery systems.

Evaluation of machine learning algorithms to predict the hydrodynamic radii and transition temperatures of chemo-biologically synthesized copolymers.

Elastin-like polypeptides (ELP) belong to a family of recombinant polymers that shows great promise as biocompatible drug delivery and tissue engineering materials. ELPs aggregate above a characteristic transition temperature (Tt). We have previously shown that the Tt and size of the resulting aggregates can be controlled by changing the ELP's solution environment (polymer concentration, salt concentration, and pH). When coupled to a synthetic polyelectrolyte, polyethyleneimine (PEI), ELP retains its Tt behavior and gains the ability to be crosslinked into defined particle sizes. This paper explores several machine learning models to predict the Tt and hydrodynamic radius (Rh) of ELP and two ELP-PEI polymers in varying solution conditions. An exhaustive design of experiments matrix consisting of 81 conditions of interest with varying salt concentration (0, 0.2, 1 M NaCl), pH (3, 7, 10), polymer concentration (0.1, 0.17, 0.3 mg/mL), and polymer type (ELP, ELP-PEI800, ELP-PEI10K) was investigated. The five models used in this study were multiple linear regression, elastic-net, support vector regression, multi-layer perceptron, and random forest. A multi-layer perceptron model was found to have the highest accuracy, with an R2 score of 0.97 for both Rh and Tt. This was followed closely by the random forest model, with an R2 of 0.94 for Rh and 0.95 for Tt. Feature importance was determined using the random forest and linear regression models. Both models showed that salt concentration and polymer type were the two most influential factors that determined Rh, while salt concentration was the dominant factor for Tt.

Comparison of the formation, adipogenic maturation, and retention of human adipose-derived stem cell spheroids in scaffold-free culture techniques.

While three-dimensional spheroids outperform traditional two-dimensional monolayer culture for human adipose-derived stem cells (hASCs), there is not a consensus on the most successful method for enhancing their adipogenic differentiation and minimizing the loss of physiologically relevant, fatty spheroids during culture. To this end, we compared three culture methods, namely, elastin-like polypeptide-polyethyleneimine (ELP-PEI) coated surfaces, ultra-low attachment static culture, and suspension culture for their ability to form and retain productive hASC spheroids. The ELP-PEI coatings used the ELP conjugated to two molecular weights of PEI (800 or 25,000 g/mol). FTIR spectroscopy, atomic force microscopy, and contact angle goniometry revealed that the ELP-PEI coatings had similar chemical structures, surface topography, and hydrophobicity. Time-lapse microscopy showed that increasing the PEI molecular weight resulted in smaller spheroids. Measurement of triglyceride content showed that the three methods induced comparable differentiation of hASCs toward the adipogenic lineage. DNA content and morphometric analysis revealed merging of spheroids to form larger spheroids in the ultra-low attachment static culture and suspension culture methods. In contrast, the retention of hASC spheroid sizes and numbers with a regular spheroid size (~100 µm) were best atop the ELP-PEI800 coatings. Overall, this research shows that the spheroid culture atop the ELP-PEI coatings is a suitable cell culture model for future studies involving long-term, three-dimensional culture of mature adipocytes derived from hASCs.

FT-IR Spectroscopic Analysis of the Secondary Structures Present during the Desiccation Induced Aggregation of Elastin-Like Polypeptide on Silica.

Previously, we found that elastin-like polypeptide (ELP), when dried above the lower critical solution temperature on top of a hydrophilic fused silica disk, exhibited a dynamic coalescence behavior. The ELP initially wet the silica, but over the next 12 h, dewett the surface and formed aggregates of precise sizes and shapes. Using Fourier-transform infrared (FT-IR) spectroscopy, the present study explores the role of secondary structures present in ELP during this progressive desiccation and their effect on aggregate size. The amide I peak (1600-1700 cm-1) in the ELP's FT-IR spectrum was deconvoluted using the second derivative method into eight subpeaks (1616, 1624, 1635, 1647, 1657, 1666, 1680, 1695 cm-1). These peaks were identified to represent extended strands, ß-turns, 3(10)-helix, polyproline I, and polyproline II using previous studies on ELP and molecules similar in peptide composition. Positive correlations were established between the various subpeaks, water content, and aggregate size to understand the contributions of the secondary structures in particle formation. The positive correlations suggest that type II ß-turns, independent of the water content, contributed to the growth of the aggregates at earlier time points (1-3.5 h). At later time points (6-12 h), the aggregate growth was attributed to the formation of 3(10)-helices that relied on a decrease in water content. Understanding these relationships gives greater control in creating precisely sized aggregates and surface coatings with varying roughness.

Rapid development of telehealth capabilities within pediatric patient portal infrastructure for COVID-19 care: barriers, solutions, results.

The COVID-19 national emergency has led to surging care demand and the need for unprecedented telehealth expansion. Rapid telehealth expansion can be especially complex for pediatric patients. From the experience of a large academic medical center, this report describes a pathway for efficiently increasing capacity of remote pediatric enrollment for telehealth while fulfilling privacy, security, and convenience concerns. The design and implementation of the process took 2 days. Five process requirements were identified: efficient enrollment, remote ability to establish parentage, minimal additional work for application processing, compliance with guidelines for adolescent autonomy, and compliance with institutional privacy and security policies. Weekly enrollment subsequently increased 10-fold for children (age 0-12 years) and 1.2-fold for adolescents (age 13-17 years). Weekly telehealth visits increased 200-fold for children and 90-fold for adolescents. The obstacles and solutions presented in this report can provide guidance to health systems for similar challenges during the COVID-19 response and future disasters.

4'-Phosphopantetheine corrects CoA, iron, and dopamine metabolic defects in mammalian models of PKAN.

Pantothenate kinase-associated neurodegeneration (PKAN) is an inborn error of CoA metabolism causing dystonia, parkinsonism, and brain iron accumulation. Lack of a good mammalian model has impeded studies of pathogenesis and development of rational therapeutics. We took a new approach to investigating an existing mouse mutant of Pank2 and found that isolating the disease-vulnerable brain revealed regional perturbations in CoA metabolism, iron homeostasis, and dopamine metabolism and functional defects in complex I and pyruvate dehydrogenase. Feeding mice a CoA pathway intermediate, 4'-phosphopantetheine, normalized levels of the CoA-, iron-, and dopamine-related biomarkers as well as activities of mitochondrial enzymes. Human cell changes also were recovered by 4'-phosphopantetheine. We can mechanistically link a defect in CoA metabolism to these secondary effects via the activation of mitochondrial acyl carrier protein, which is essential to oxidative phosphorylation, iron-sulfur cluster biogenesis, and mitochondrial fatty acid synthesis. We demonstrate the fidelity of our model in recapitulating features of the human disease. Moreover, we identify pharmacodynamic biomarkers, provide insights into disease pathogenesis, and offer evidence for 4'-phosphopantetheine as a candidate therapeutic for PKAN.

Policies and procedures governing patient portal use at an Academic Medical Center.

BACKGROUND AND OBJECTIVE: Patient portal use has increased over the last two decades in response to consumer demand and government regulation. Despite growing adoption, few guidelines exist to direct successful implementation and governance. We describe the policies and procedures that have governed over a decade of continuous My Health at Vanderbilt (MHAV) patient portal use. METHODS: We examined MHAV usage data between May 2007 and November 2017. We classified patient portal activity into eight functional categories: Appointment, Billing, Document Access, Genetics, Health Result, Immunization, Medication, and Messaging. We describe our operating policies and measure portal uptake, patient account activity, and function use over time. RESULTS: By the end of the study period, there were 375 517 registered accounts. Policies made MHAV available to competent adults and adolescents 13 and over. Patients signed up for a limited access account online, which could be upgraded to a full-access account after identity verification. Patients could assign proxy accounts to family and caregivers, which permitted nonpatient access to select MHAV functions. Laboratory and radiology results were accessible via MHAV. Results were classified into three groups based on sensitivity, which govern the length of delay before results appeared in MHAV. DISCUSSION AND CONCLUSION: Patient portals offer significant opportunity to engage patients in their healthcare. However, there remains a need to understand how policies can promote uptake and use. We anticipate that other institutions can apply concepts from our policies to support meaningful patient portal engagement.

Visualization of the temperature dependent rearrangement of SynB1 elastin-like polypeptide on silica using scanning electron microscopy.

In this study, scanning electron microscopy (SEM) was used to observe the interaction between de-solvated SynB1-elastin-like polypeptide (SynB1-ELP) and silica at a temperature above ELP's lower critical solution temperature (LCST). ELP was seen to initially wet the surface of the silica before rearranging to form narrowly distributed spherical particles. After formation, the ELP particles dynamically rearranged to increase and subsequently decrease in size until 24 h at which time they collapsed. SEM and Energy Dispersive X-ray Spectroscopy revealed that the formation of a thin layer of salt from the PBS solution preceded the initial wetting of ELP on silica, which was shown to play a role in the continuous rearrangement of ELP. FT-IR revealed that the salt, in combination with the hydrophilic silica, trapped water that provided a repulsive surface to the hydrophobic ELP and forced the ELP to continuously minimize its surface area until the water evaporated. This behavior shows that ELP's thermo-responsive nature coupled with its hydrophobicity can be used to create ELP particles and surfaces that can reorganize with minimal water present.

Exchange-mediated contrast in CEST and spin-lock imaging.

PURPOSE: Magnetic resonance images of biological media based on chemical exchange saturation transfer (CEST) show contrast that depends on chemical exchange between water and other protons. In addition, spin-lattice relaxation rates in the rotating frame (R1ρ) are also affected by exchange, especially at high fields, and can be exploited to provide novel, exchange-dependent contrast. Here, we evaluate and compare the factors that modulate the exchange contrast for these methods using simulations and experiments on simple, biologically relevant samples. METHODS: Simulations and experimental measurements at 9.4 T of rotating frame relaxation rate dispersion and CEST contrast were performed on solutions of macromolecules containing amide and hydroxyl exchanging protons. RESULTS: The simulations and experimental measurements confirm that both CEST and R1ρ measurements depend on similar exchange parameters, but they manifest themselves differently in their effects on contrast. CEST contrast may be larger in the slow and intermediate exchange regimes for protons with large resonant frequency offsets (e.g. >2 ppm). Spin-locking techniques can produce larger contrast enhancement when resonant frequency offsets are small (<2 ppm) and exchange is in the intermediate-to-fast regime. The image contrasts scale differently with field strength, exchange rate and concentration. CONCLUSION: CEST and R1ρ measurements provide different and somewhat complementary information about exchange in tissues. Whereas CEST can depict exchange of protons with specific chemical shifts, appropriate R1ρ-dependent acquisitions can be employed to selectively portray protons of specific exchange rates.

Reduction in the number and associated costs of unindicated dual-phase head CT examinations after a quality improvement initiative.

OBJECTIVE: During this study, we instituted a phased quality improvement initiative designed to educate referring clinicians and departmental radiologists about the recommendations of the American College of Radiology (ACR) Appropriateness Criteria for dual-phase (without and with contrast material) head CT examinations. The primary aims of the study were to evaluate whether the quality improvement initiative was associated with an improvement in ACR Appropriateness Criteria appropriateness ratings and a reduction in the number of unindicated dual-phase head CT examinations performed. A secondary aim was to assess the impact of the quality improvement initiative on health care costs. MATERIALS AND METHODS: This study included-with the exception of the examinations performed during a 3-month training period-all single- and dual-phase head CT examinations performed of adult patients at a tertiary care medical center from January 2009 through October 2011. Both inpatients and outpatient examinations were included. There were no exclusion criteria. RESULTS: Implementation of the initiative enhanced patient safety and reduced health care costs by achieving a significant reduction (p = 0.006) in the number of unindicated dual-phase head CT examinations performed from a median number of 40 per month to 17 per month. CONCLUSION: Although there are potential benefits for dual-phase head CT examinations, the medical and economic risks should be measured against these potential benefits. Incorporating the ACR Appropriateness Criteria applies evidence-based medicine to this algorithm. In this outcomes-driven study, the number of unindicated dual-phase head CT examinations was reduced and imaging efficacy improved primarily through physician education and monitoring.

T1ρ mapping of pediatric epiphyseal and articular cartilage in the knee.

PURPOSE: To evaluate the feasibility of measuring T1ρ values in epiphyseal cartilage in children, we have conducted a novel study of spin locking techniques. Adult articular cartilage has been widely studied with spin locking techniques by magnetic resonance imaging. However, no results are available for in vivo T1ρ imaging of developing cartilage. MATERIALS AND METHODS: Ten volunteers of age 6 ± 3 years were recruited to have T1ρ mapping performed on the knee at the conclusion of their clinical study. T1ρ maps were generated using a spin-lock cluster followed by a fast spin-echo imaging sequence. Regions of interest (ROIs) were placed in non-load-bearing (NLB), load-bearing (LB), and articular cartilage. RESULTS: Student's t-tests were performed to compare means among the ROIs. Mean T1ρ for epiphyseal and articular cartilage was 49.8 ± 9 and 76.6 ± 7 ms, respectively. LB and NLB T1ρ vales were 47.1 ± 9.5 and 52.5 ± 9 ms, respectively. Significant differences were found in T1ρ values between epiphyseal and articular cartilage layers (P = 0.0001). No difference in T1ρ was observed between NLB and LB layers. A modest trend was also noted for epiphyseal and articular cartilage regions with age. CONCLUSION: It is feasible to quantify differences in epiphyseal and articular cartilage layers with SL techniques. T1ρ holds promise as a noninvasive method of studying normal and abnormal developmental states of cartilage in children.

Contributions of chemical and diffusive exchange to T1ρ dispersion.

Variations in local magnetic susceptibility may induce magnetic field gradients that affect the signals acquired for MR imaging. Under appropriate diffusion conditions, such fields produce effects similar to slow chemical exchange. These effects may also be found in combination with other chemical exchange processes at multiple time scales. We investigate these effects with simulations and measurements to determine their contributions to rotating frame (R1ρ ) relaxation in model systems. Simulations of diffusive and chemical exchange effects on R1ρ dispersion were performed using the Bloch equations. Additionally, R1ρ dispersion was measured in suspensions of Sephadex and latex beads with varying spin locking fields at 9.4 T. A novel analysis method was used to iteratively fit for apparent chemical and diffusive exchange rates with a model by Chopra et al. Single- and double-inflection points in R1ρ dispersion profiles were observed, respectively, in simulations of slow diffusive exchange alone and when combined with rapid chemical exchange. These simulations were consistent with measurements of R1ρ in latex bead suspensions and small-diameter Sephadex beads that showed single- and double-inflection points, respectively. These observations, along with measurements following changes in temperature and pH, are consistent with the combined effects of slow diffusion and rapid -OH exchange processes.

Exchange-mediated contrast agents for spin-lock imaging.

Measurements of relaxation rates in the rotating frame with spin-locking techniques are sensitive to substances with exchanging protons with appropriate chemical shifts. The authors develop a novel approach to exchange-rate selective imaging based on measured T(1ρ) dispersion with applied locking field strength, and demonstrate the method on samples containing the X-ray contrast agent Iohexol with and without cross-linked bovine serum albumin. T(1ρ) dispersion of water in the phantoms was measured with a Varian 9.4-T magnet by an on-resonance spin-locking pulse with fast spin-echo readout, and the results used to estimate exchange rates. The Iohexol phantom alone gave a fitted exchange rate of ~1 kHz, bovine serum albumin alone was ~11 kHz, and in combination gave rates in between. By using these estimated rates, we demonstrate how a novel spin-locking imaging method may be used to enhance contrast due to the presence of a contrast agent whose protons have specific exchange rates.

Contributions of chemical exchange to T1ρ dispersion in a tissue model.

Variations in T(1ρ) with locking-field strength (T(1ρ) dispersion) may be used to estimate proton exchange rates. We developed a novel approach utilizing the second derivative of the dispersion curve to measure exchange in a model system of cross-linked polyacrylamide gels. These gels were varied in relative composition of comonomers, increasing stiffness, and in pH, modifying exchange rates. Magnetic resonance images were recorded with a spin-locking sequence as described by Sepponen et al. These measurements were fit to a mono-exponential decay function yielding values for T(1ρ) at each locking-field measured. These values were then fit to a model by Chopra et al. for estimating exchange rates. For low stiffness gels, the calculated exchange values increased by a factor of 4 as pH increased, consistent with chemical exchange being the dominant contributor to T(1ρ) dispersion. Interestingly, calculated chemical exchange rates also increased with stiffness, likely due to modified side-chain exchange kinetics as the composition varied. This article demonstrates a new method to assess the structural and chemical effects on T(1ρ) relaxation dispersion with a suitable model. These phenomena may be exploited in an imaging context to emphasize the presence of nuclei of specific exchange rates, rather than chemical shifts.