An audio personal health library of clinic visit recordings for patients and their caregivers (HealthPAL): User-centered design approach

Background: Providing digital recordings of clinic visits to patients has emerged as a strategy to promote patient and family engagement in care. With advances in natural language processing, an opportunity exists to maximize the value of visit recordings for patients by automatically tagging key visit information (eg, medications, tests, and imaging) and linkages to trustworthy web-based resources curated in an audio-based personal health library. Objective: This study aims to report on the user-centered development of HealthPAL, an audio personal health library. Methods: Our user-centered design and usability evaluation approach incorporated iterative rounds of video-recorded sessions from 2016 to 2019. We recruited participants from a range of community settings to represent older patient and caregiver perspectives. In the first round, we used paper prototypes and focused on feature envisionment. We moved to low-fidelity and high-fidelity versions of the HealthPAL in later rounds, which focused on functionality and use; all sessions included a debriefing interview. Participants listened to a deidentified, standardized primary care visit recording before completing a series of tasks (eg, finding where a medication was discussed in the recording). In the final round, we recorded the patients\u27 primary care clinic visits for use in the session. Findings from each round informed the agile software development process. Task completion and critical incidents were recorded in each round, and the System Usability Scale was completed by participants using the digital prototype in later rounds. Results: We completed 5 rounds of usability sessions with 40 participants, of whom 25 (63%) were women with a median age of 68 years (range 23-89). Feedback from sessions resulted in color-coding and highlighting of information tags, a more prominent play button, clearer structure to move between one\u27s own recordings and others\u27 recordings, the ability to filter recording content by the topic discussed and descriptions, 10-second forward and rewind controls, and a help link and search bar. Perceived usability increased over the rounds, with a median System Usability Scale of 78.2 (range 20-100) in the final round. Participants were overwhelmingly positive about the concept of accessing a curated audio recording of a clinic visit. Some participants reported concerns about privacy and the computer-based skills necessary to access recordings. Conclusions: To our knowledge, HealthPAL is the first patient-centered app designed to allow patients and their caregivers to access easy-to-navigate recordings of clinic visits, with key concepts tagged and hyperlinks to further information provided. The HealthPAL user interface has been rigorously co-designed with older adult patients and their caregivers and is now ready for further field testing. The successful development and use of HealthPAL may help improve the ability of patients to manage their own care, especially older adult patients who have to navigate complex treatment plans

A proteasome inhibitor, bortezomib, inhibits breast cancer growth and reduces osteolysis by downregulating metastatic genes

PURPOSE: The incidence of bone metastasis in advanced breast cancer (BrCa) exceeds 70%. Bortezomib, a proteasome inhibitor used for the treatment of multiple myeloma, also promotes bone formation. We tested the hypothesis that proteasome inhibitors can ameliorate BrCa osteolytic disease. EXPERIMENTAL DESIGN: To address the potentially beneficial effect of bortezomib in reducing tumor growth in the skeleton and counteracting bone osteolysis, human MDA-MB-231 BrCa cells were injected into the tibia of mice to model bone tumor growth for in vivo assessment of treatment regimens before and after tumor growth. RESULTS: Controls exhibited tumor growth, destroying trabecular and cortical bone and invading muscle. Bortezomib treatment initiated following inoculation of tumor cells strikingly reduced tumor growth, restricted tumor cells mainly to the marrow cavity, and almost completely inhibited osteolysis in the bone microenvironment over a 3- to 4-week period as shown by [(18)F]fluorodeoxyglucose positron emission tomography, micro-computed tomography scanning, radiography, and histology. Thus, proteasome inhibition is effective in killing tumor cells within the bone. Pretreatment with bortezomib for 3 weeks before inoculation of tumor cells was also effective in reducing osteolysis. Our in vitro and in vivo studies indicate that mechanisms by which bortezomib inhibits tumor growth and reduces osteolysis result from inhibited cell proliferation, necrosis, and decreased expression of factors that promote BrCa tumor progression in bone. CONCLUSION: These findings provide a basis for a novel strategy to treat patients with BrCa osteolytic lesions, and represent an approach for protecting the entire skeleton from metastatic bone disease

Pharmacologic targeting of a stem/progenitor population in vivo is associated with enhanced bone regeneration in mice

Drug targeting of adult stem cells has been proposed as a strategy for regenerative medicine, but very few drugs are known to target stem cell populations in vivo. Mesenchymal stem/progenitor cells (MSCs) are a multipotent population of cells that can differentiate into muscle, bone, fat, and other cell types in context-specific manners. Bortezomib (Bzb) is a clinically available proteasome inhibitor used in the treatment of multiple myeloma. Here, we show that Bzb induces MSCs to preferentially undergo osteoblastic differentiation, in part by modulation of the bone-specifying transcription factor runt-related transcription factor 2 (Runx-2) in mice. Mice implanted with MSCs showed increased ectopic ossicle and bone formation when recipients received low doses of Bzb. Furthermore, this treatment increased bone formation and rescued bone loss in a mouse model of osteoporosis. Thus, we show that a tissue-resident adult stem cell population in vivo can be pharmacologically modified to promote a regenerative function in adult animals