Determining patient preferences for the medical management of osteoporosis using conjoint analysis.

We used conjoint analysis-a method that assesses complex decision making-to quantify patients' choices when selecting an osteoporosis therapy. While 60% of people prioritized medication efficacy when deciding among treatments, the remaining 40% highly valued factors other than efficacy, suggesting the need for personalized shared decision-making tools. INTRODUCTION: In this study, we aimed to examine patient decision-making surrounding osteoporosis medications using conjoint analysis. METHODS: We enrolled osteoporosis patients at an academic medical center to complete an online conjoint exercise which calculated each patient's relative importance score of 6 osteoporosis medication attributes (higher = greater relative importance in decision-making). We used latent class analysis to identify distinct segments of patients with similar choice patterns and then used logistic regression to determine if demographics and osteoporosis disease features were associated with latent class assignment. RESULTS: Overall, 304 participants completed the survey. The rank order of medication attributes by importance score was the following: efficacy at preventing hip fractures (accounted for 31.0% of decision making), mode of administration (17.5%); risk of serious side effects (16.6%); dose frequency (13.9%); efficacy at preventing spine fractures (12.5%); risk of non-serious side effects (8.4%). We found that 60.9% of the cohort prioritized medication efficacy as their top factor when selecting among the therapies. Being a college graduate, having stronger beliefs on the necessity of using medications for osteoporosis, and never having used osteoporosis medicines were the only factors associated with prioritizing medication efficacy for fracture prevention over the other factors in the decision-making process. CONCLUSIONS: While about 60% of patients prioritized efficacy when selecting an osteoporosis therapy, the remaining 40% valued other factors more highly. Furthermore, individual patient characteristics and clinical factors did not reliably predict patient decision making, suggesting that development and implementation of shared decision-making tools is warranted.

Slow-motion smartphone video improves interobserver reliability of gait assessment in ambulatory cerebral palsy.

Purpose: Structured visual gait assessment is essential for the evaluation of pediatric patients with neuromuscular conditions. The purpose of this study was to evaluate the benefit of slow-motion video recorded on a standard smartphone to augment visual gait assessment. Methods: Coronal and sagittal plane videos of the gait of five pediatric subjects were recorded on a smartphone, including four subjects with ambulatory cerebral palsy and one subject without gait pathology. Twenty-one video scorers were recruited and randomized to evaluate slow-motion or normal-speed videos utilizing the Edinburgh Visual Gait Score. The slow-motion group (N = 11) evaluated the videos at one-eighth speed, and the normal-speed group (N = 10) evaluated the same videos at normal speed. Interrater reliabilities were determined by calculating intraclass correlation coefficients for each group as a whole, for each Edinburgh Visual Gait Score item, and after stratification by evaluator experience level. Results: The slow-motion group exhibited an intraclass correlation coefficient of 0.65 (95% confidence interval: 0.58-0.73), whereas the normal-speed group exhibited an intraclass correlation coefficient of 0.57 (95% confidence interval: 0.49-0.65). For less-experienced scorers, intraclass correlation coefficients of 0.62 (95% confidence interval: 0.53-0.71) and 0.50 (95% confidence interval: 0.40-0.59) were calculated for slow motion and normal speed, respectively. For more-experienced scorers, intraclass correlation coefficients of 0.69 (95% confidence interval: 0.61-0.76) and 0.67 (95% confidence interval: 0.58-0.75) were calculated for slow motion and normal speed, respectively. Conclusions: Visual gait assessment is enhanced by the use of slow-motion smartphone video, a tool widely available throughout the world with no marginal cost. Level of evidence: level I, randomized study.

Patient Preferences for Colorectal Cancer Screening Tests in Light of Lowering the Screening Age to 45 Years.

BACKGROUND & AIMS: In 2021, the US Preventive Services Task Force lowered the colorectal cancer (CRC) screening age to 45 years. We used conjoint analysis, a method that assesses complex decision making, to update our understanding on people's CRC screening test preferences in the context of new guidelines. METHODS: We conducted a conjoint analysis survey among unscreened individuals ≥40 years at average risk for CRC to determine the relative importance of screening test attributes in their decision making (eg, modality, effectiveness at reducing CRC risk, bowel prep). We also performed simulations to estimate the proportion of people who would prefer each US Multi-Society Task Force (MSTF) on CRC-recommended test. The analyses were stratified among those aged 40-49 years (newly or soon-to-be eligible for screening) and ≥50 years (have been eligible). RESULTS: Overall, 1000 participants completed the conjoint analysis (40-49 years, n = 456; ≥50 years, n = 544). When considering all 5 US MSTF-recommended tests, there were differences in test preferences between age groups (P = .019), and the most preferred test was a fecal immunochemical test (FIT)-fecal DNA every 3 years: 40-49 years, 34.6%; ≥50 years, 37.3%. When considering only the US MSTF tier 1 tests, most 40- to 49- (68.9%) and ≥50-year-olds (77.4%; P = .004) preferred an annual FIT over a colonoscopy every 10 years. CONCLUSIONS: Our findings suggest that more than one-third of people may want to do a FIT-fecal DNA every 3 years for their CRC screening. When only considering US MSTF tier 1 tests, three-fourths of people may prefer an annual FIT over colonoscopy. Further research examining CRC screening test preferences among broader populations is warranted to inform and enhance screening programs.

Fecal immunochemical test (FIT) versus colonoscopy: Does knowing that a positive FIT requires a follow-up colonoscopy affect initial decision making in the US?

Although many people prefer fecal immunochemical test (FIT) over colonoscopy due to its noninvasive nature, it is unclear whether FIT would still be preferred for colorectal cancer (CRC) screening if they were explicitly informed that + FIT requires follow-up colonoscopy. To address this gap, we administered two conjoint analysis surveys-one that explained the need for a follow-up colonoscopy after + FIT while the other did not-to a US nationwide sample of Americans and then assessed whether there were differences in colonoscopy/FIT preferences between cohorts. We recruited adults ≥ 40yo who had not undergone CRC screening via an online survey research firm. We deployed two surveys that used conjoint analysis to assess decision making surrounding CRC screening tests: Survey 1 (4/2-4/15/2021)-did not inform participants that they need a colonoscopy following a + FIT; Survey 2 (4/29-6/2/2021)-informed respondents of the potential need. Using the conjoint analysis data, we determined the proportion of those who preferred FIT or colonoscopy and then used logistic regression to assess for differences in colonoscopy/FIT preferences between the cohorts. Overall, 501 and 1,000 individuals completed Survey 1 (without description of need for colonoscopy after + FIT) and Survey 2 (with description), respectively. There was no difference in test preference between cohorts after adjusting for covariates in the logistic regression (adjusted p = 0.09): Survey 1 (without description)-colonoscopy 28.5%, FIT 71.5%; Survey 2 (with description)-colonoscopy 26.7%, FIT 73.3%. Thus, knowledge that a + FIT requires a follow-up colonoscopy does not alter people's strong preference for non-invasive stool testing with FIT.

Qualitative Validation of a Novel VR Program for Irritable Bowel Syndrome: A VR1 Study.

INTRODUCTION: Although gut-directed psychotherapies are effective for irritable bowel syndrome (IBS), they are rarely prescribed, given a paucity of trained clinicians. Virtual reality (VR) offers a solution by allowing patients to self-practice these techniques in a standardized manner. METHODS: A multidisciplinary team developed IBS/VR, a program that transports users into immersive VR worlds that teach patients about the brain-gut axis, cognitive behavioral therapy, and gut-directed meditation. We tested IBS/VR in Rome IV IBS patients and used inductive analysis to evaluate perceptions and identify recommendations. RESULTS: We achieved thematic saturation after 9 interviews; 3 additional interviews revealed no emergent themes. After making 23 software changes based on patient feedback, we conducted 3 additional interviews which confirmed thematic saturation (N = 15 total). DISCUSSION: This study offers initial validation of the first VR program designed for IBS.

Home-based virtual reality for chronic pain: protocol for an NIH-supported randomised-controlled trial.

INTRODUCTION: Chronic pain is highly prevalent and associated with a large burden of illness; there is a pressing need for safe, home-based, non-pharmacological, interventions. Virtual reality (VR) is a digital therapeutic known to be effective for acute pain, but its role in chronic pain is not yet fully elucidated. Here we present a protocol for the National Institute of Health (NIH) Back Pain Consortium (BACPAC) VR trial that evaluates the effectiveness of three forms of VR for patients with chronic lower back pain (cLBP), a highly prevalent form of chronic pain. METHODS AND ANALYSIS: The NIH BACPAC VR trial will randomise 360 patients with cLBP into one of three arms, each administered through a head-mounted display: 1) skills-based VR, a program incorporating principles of cognitive behavioural therapy, mindful meditation and physiological biofeedback therapy using embedded biometric sensors; 2) distraction-based VR, a program using 360-degree immersive videos designed to distract users from pain; and 3) sham VR, a non-immersive program using two-dimensional videos within a VR headset. Research participants will be monitored for 12 weeks using a combination of patient-reported outcomes administered via REDCap (Research Electronic Data Capture), wearable sensor data collected via Fitbit Charge 4 and electronic health record data. The primary outcome will be the NIH Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference scale. Secondary outcomes will include PROMIS Anxiety, PROMIS Sleep Disturbance, opioid prescription data and Pain Catastrophizing Scale Short Form. A subgroup analysis will explore patient level predictors for VR efficacy. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Institutional Review Board of Cedars-Sinai Health System in April 2020. The results will be disseminated in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT04409353.

Home Visits Improve Attitudes and Self-Efficacy: A Longitudinal Curriculum for Residents.

OBJECTIVES: To develop a competency-based, adaptable home visit curricula and clinical framework for family medicine (FM) residents, and to examine resident attitudes, self-efficacy, and skills following implementation. DESIGN: Quantitative analysis of resident survey responses and qualitative thematic analysis of written resident reflections. SETTING: Urban FM residency program. PARTICIPANTS: A total of 43 residents and 20 homebound patients in a home-based primary care program. INTERVENTION: A home-based primary care practice and accompanying curriculum for FM residents was developed and implemented to improve learners' confidence and skills to perform home visits. MEASUREMENTS: A 10-question survey with a 4-point Likert scale and open-ended responses. Written resident reflections following home visits. RESULTS: Over 3 years, 43 unique respondents completed a total of 79 surveys evaluating attitudes, skills, and barriers to home care. Some residents may have completed the survey more than once at different stages in their training. Overall, 86% are interested in home visits in future practice, and 78% of survey responses indicated an increased likelihood to perform home visits with more training. Learners with two or more home visits reported significantly improved confidence. Themes across all resident reflections included social determinants of health, patient-physician relationship, patient-home assessment, patient autonomy/independence, and physician wellness/attitudes. Residents described how home visits encourage more holistic care to improve outcomes for patients who are homebound. CONCLUSION: Our home visit curriculum provided new learning, an enhanced desire to practice home-based primary care, improved learner confidence, and could help residents meet the need of a growing population of adults who are homebound. J Am Geriatr Soc 68:852-858, 2020.

Polymer Conjugation to Enhance Cellulase Activity and Preserve Thermal and Functional Stability.

A thermophilic cellulase, FnCel5a, from Fervidobacterium nodosum was conjugated with various functional polymers including cationic, anionic, and strongly and weakly hydrogen bonding polymers. The activity of FnCel5a toward a high-molecular-weight carboxymethyl cellulose substrate was enhanced by polymer conjugation. Activity enhancements of 50% or greater observed for acrylamide and mixed N,N-dimethyl acrylamide-2-(N,N-dimethylamino)ethyl methacrylate polymers, suggesting that the greatest enhancements were caused by polymers capable of noncovalent interactions with the substrate. The conjugates were found to have nearly identical thermodynamic stability to the native enzyme, as assessed by free energy (ΔG), enthalpy (ΔH), and entropy (TΔS) parameters extracted from differential scanning fluorimetry. Polymers tended to confer comparable tolerance to high concentrations of dimethylformamide, with longer polymers typically enabling higher activity relative to shorter polymers. The new FnCel5a conjugates represent an advance in the production of cellulases that maintain activity at high temperatures or in the presence of denaturing organic solvents.

Strategies for Biophysical Characterization of Protein-Polymer Conjugates.

Protein-polymer conjugates are increasingly viewed as promising avenues to producing industrial enzymes with high activity capable of withstanding potentially harsh reaction conditions, or to designing novel therapeutics with triggered release, controlled masking, or increased resistance to proteolytic degradation. Common among these applications are the desire to improve the stability of protein-polymer conjugates to unfolding by exposure to chemicals or thermal stress. Thus, assays that allow researchers to robustly and easily characterize protein-polymer conjugates by obtaining thermodynamic parameters for folding stand to play an important role in the development of improved protein-polymer conjugates. Herein, we describe two techniques, differential scanning fluorimetry and intrinsic tryptophan fluorescence, used in our laboratories to obtain thermodynamic parameters of unfolding that allow for direct comparison of protein-polymer conjugates and the myriad effects of variations in attachment site, polymer identity, and polymer length. These two experiments, which are easily amenable to parallelization, are presented as high-throughput replacements for more traditionally employed circular dichroism experiments and as complements to functional chemical stability or functional thermal stability experiments. Each assay is presented in a parallelized format that allows for rapid scaling and high-throughput analysis of protein-polymer conjugate libraries. Descriptions of the assays include a discussion of advantages and disadvantages alongside protocol details and approaches to data analysis.

Investigating the Impact of Polymer Functional Groups on the Stability and Activity of Lysozyme-Polymer Conjugates.

Polymers are often conjugated to proteins to improve stability; however, the impact of polymer chain length and functional groups on protein structure and function is not well understood. Here we use RAFT polymerization to grow polymers of different lengths and functionality from a short acrylamide oligomer with a RAFT end group conjugated to lysozyme. We show by X-ray crystallography that enzyme structure is minimally impacted by modification with the RAFT end group. Significant activity toward the negatively charged Micrococcus lysodeicticus cell wall was maintained when lysozyme was modified with cationic polymers. Thermal and chemical stability of the conjugates was characterized using differential scanning fluorimetry and tryptophan fluorescence. All conjugates had a lower melting temperature; however, conjugates containing ionic or substrate mimicking polymers were more resistant to denaturation by guanidine hydrochloride. Our results demonstrate that tailoring polymer functionality can improve conjugate activity and minimize enzymatic inactivation by denaturants.

Well-Defined Macromolecules Using Horseradish Peroxidase as a RAFT Initiase.

Enzymatic catalysis and control over macromolecular architectures from reversible addition-fragmentation chain transfer polymerization (RAFT) are combined to give a new method of making polymers. Horseradish peroxidase (HRP) is used to catalytically generate radicals using hydrogen peroxide and acetylacetone as a mediator. RAFT is used to control the polymer structure. HRP catalyzed RAFT polymerization gives acrylate and acrylamide polymers with relatively narrow molecular weight distributions. The polymerization is rapid, typically exceeding 90% monomer conversion in 30 min. Complex macromolecular architectures including a block copolymer and a protein-polymer conjugate are synthesized using HRP to catalytically initiate RAFT polymerization.

Metal Ion Dependence of the Matrix Metalloproteinase-1 Mechanism.

Matrix metalloproteinase-1 (MMP-1) plays crucial roles in disease-related physiologies and pathological processes in the human body. We report here solution studies of MMP-1, including characterization of a series of mutants designed to bind metal in either the catalytic site or the structural site (but not both). Circular dichroism and fluorescence spectroscopy of the mutants demonstrate the importance of the structural Zn(II) in maintaining both secondary and tertiary structure, while UV-visible, nuclear magnetic resonance, electron paramagnetic resonance, and extended X-ray absorption fine structure show its presence influences the catalytic metal ion's coordination number. The mutants allow us to demonstrate convincingly the preparation of a mixed-metal analogue, Co(C)Zn(S)-MMP-1, with Zn(II) in the structural site and Co(II) in the catalytic site. Stopped-flow fluorescence of the native form, Zn(C)Zn(S)-MMP-1, and the mixed-metal Co(C)Zn(S)-MMP-1 analogue shows that the internal fluorescence of a nearby Trp residue is modulated with catalysis and can be used to monitor reactivity under a number of conditions, opening the door to substrate profiling.