Impact of an Electronic Health Record-Integrated Personal Health Record on Patient Participation in Health Care: Development and Randomized Controlled Trial of MyHealthKeeper.

BACKGROUND: Personal health record (PHR)-based health care management systems can improve patient engagement and data-driven medical diagnosis in a clinical setting. OBJECTIVE: The purpose of this study was (1) to demonstrate the development of an electronic health record (EHR)-tethered PHR app named MyHealthKeeper, which can retrieve data from a wearable device and deliver these data to a hospital EHR system, and (2) to study the effectiveness of a PHR data-driven clinical intervention with clinical trial results. METHODS: To improve the conventional EHR-tethered PHR, we ascertained clinicians' unmet needs regarding PHR functionality and the data frequently used in the field through a cocreation workshop. We incorporated the requirements into the system design and architecture of the MyHealthKeeper PHR module. We constructed the app and validated the effectiveness of the PHR module by conducting a 4-week clinical trial. We used a commercially available activity tracker (Misfit) to collect individual physical activity data, and developed the MyHealthKeeper mobile phone app to record participants' patterns of daily food intake and activity logs. We randomly assigned 80 participants to either the PHR-based intervention group (n=51) or the control group (n=29). All of the study participants completed a paper-based survey, a laboratory test, a physical examination, and an opinion interview. During the 4-week study period, we collected health-related mobile data, and study participants visited the outpatient clinic twice and received PHR-based clinical diagnosis and recommendations. RESULTS: A total of 68 participants (44 in the intervention group and 24 in the control group) completed the study. The PHR intervention group showed significantly higher weight loss than the control group (mean 1.4 kg, 95% CI 0.9-1.9; P<.001) at the final week (week 4). In addition, triglyceride levels were significantly lower by the end of the study period (mean 2.59 mmol/L, 95% CI 17.6-75.8; P=.002). CONCLUSIONS: We developed an innovative EHR-tethered PHR system that allowed clinicians and patients to share lifelog data. This study shows the effectiveness of a patient-managed and clinician-guided health tracker system and its potential to improve patient clinical profiles. TRIAL REGISTRATION: ClinicalTrials.gov NCT03200119; https://clinicaltrials.gov/ct2/show/NCT03200119 (Archived by WebCite at http://www.webcitation.org/6v01HaCdd).

Small heterodimer partner blocks cardiac hypertrophy by interfering with GATA6 signaling.

RATIONALE: Small heterodimer partner (SHP; NR0B2) is an atypical orphan nuclear receptor that lacks a conventional DNA-binding domain. Through interactions with other transcription factors, SHP regulates diverse biological events, including glucose metabolism in liver. However, the role of SHP in adult heart diseases has not yet been demonstrated. OBJECTIVE: We aimed to investigate the role of SHP in adult heart in association with cardiac hypertrophy. METHODS AND RESULTS: The roles of SHP in cardiac hypertrophy were tested in primary cultured cardiomyocytes and in animal models. SHP-null mice showed a hypertrophic phenotype. Hypertrophic stresses repressed the expression of SHP, whereas forced expression of SHP blocked the development of hypertrophy in cardiomyocytes. SHP reduced the protein amount of Gata6 and, by direct physical interaction with Gata6, interfered with the binding of Gata6 to GATA-binding elements in the promoter regions of natriuretic peptide precursor type A. Metformin, an antidiabetic agent, induced SHP and suppressed cardiac hypertrophy. The metformin-induced antihypertrophic effect was attenuated either by SHP small interfering RNA in cardiomyocytes or in SHP-null mice. CONCLUSIONS: These results establish SHP as a novel antihypertrophic regulator that acts by interfering with GATA6 signaling. SHP may participate in the metformin-induced antihypertrophic response.

Engineering extracellular vesicles for ROS scavenging and tissue regeneration.

Stem cell therapy holds promise for tissue regeneration, yet significant challenges persist. Emerging as a safer and potentially more effective alternative, extracellular vesicles (EVs) derived from stem cells exhibit remarkable abilities to activate critical signaling cascades, thereby facilitating tissue repair. EVs, nano-scale membrane vesicles, mediate intercellular communication by encapsulating a diverse cargo of proteins, lipids, and nucleic acids. Their therapeutic potential lies in delivering cargos, activating signaling pathways, and efficiently mitigating oxidative stress-an essential aspect of overcoming limitations in stem cell-based tissue repair. This review focuses on engineering and applying EVs in tissue regeneration, emphasizing their role in regulating reactive oxygen species (ROS) pathways. Additionally, we explore strategies to enhance EV therapeutic activity, including functionalization and incorporation of antioxidant defense proteins. Understanding these molecular mechanisms is crucial for optimizing EV-based regenerative therapies. Insights into EV and ROS signaling modulation pave the way for targeted and efficient regenerative therapies harnessing the potential of EVs.

Casein kinase-2α1 induces hypertrophic response by phosphorylation of histone deacetylase 2 S394 and its activation in the heart.

BACKGROUND: Cardiac hypertrophy is characterized by transcriptional reprogramming of fetal gene expression, and histone deacetylases (HDACs) are tightly linked to the regulation of those genes. We previously demonstrated that activation of HDAC2, 1 of the class I HDACs, mediates hypertrophy. Here, we show that casein kinase-2α1 (CK2α1)-dependent phosphorylation of HDAC2 S394 is required for the development of cardiac hypertrophy. METHODS AND RESULTS: Hypertrophic stimuli phosphorylated HDAC2 S394, which was necessary for its enzymatic activation, and therefore the development of hypertrophic phenotypes in rat neonatal cardiomyocytes or in isoproterenol-administered mice hearts. Transgenic mice overexpressing HDAC2 wild type exhibited cardiac hypertrophy, whereas those expressing phosphorylation-resistant HDAC2 S394A did not. Compared with that in age-matched normal human hearts, phosphorylation of HDAC2 S394 was dramatically increased in patients with hypertrophic cardiomyopathy. Hypertrophy-induced phosphorylation of HDAC2 S394 and its enzymatic activity were completely blocked either by CK2 blockers or by CK2α1 short interfering RNA. Hypertrophic stimuli led CK2α1 to be activated, and its chemical inhibitors blocked hypertrophy in both phenylephrine-treated cardiomyocytes and isoproterenol-administered mice. CK2α1-transgenic mice developed hypertrophy, which was attenuated by administration of trichostatin A, an HDAC inhibitor. Overexpression of CK2α1 caused hypertrophy in cardiomyocytes, whereas chemical inhibitors of both CK2 and HDAC as well as HDAC2 S394A blunted it. Hypertrophy in CK2α1-transgenic mice was exaggerated by crossing these mice with wild-type-HDAC2-overexpressing mice. By contrast, however, it was blocked when CK2α1-transgenic mice were crossed with HDAC2 S394A-transgenic mice. CONCLUSIONS: We have demonstrated a novel mechanism in the development of cardiac hypertrophy by which CK2 activates HDAC2 via phosphorylating HDAC2 S394.

Envisioning the use of in-situ arm movement data in stroke rehabilitation: Stroke survivors' and occupational therapists' perspectives.

BACKGROUND: The key for successful stroke upper-limb rehabilitation includes the personalization of therapeutic interventions based on patients' functional ability and performance level. However, therapists often encounter challenges in supporting personalized rehabilitation due to the lack of information about how stroke survivors use their stroke-affected arm outside the clinic. Wearable technologies have been considered as an effective, objective solution to monitor patients' arm use patterns in their naturalistic environments. However, these technologies have remained a proof of concept and have not been adopted as mainstream therapeutic products, and we lack understanding of how key stakeholders perceive the use of wearable technologies in their practice. OBJECTIVE: We aim to understand how stroke survivors and therapists perceive and envision the use of wearable sensors and arm activity data in practical settings and how we could design a wearable-based performance monitoring system to better support the needs of the stakeholders. METHODS: We conducted semi-structured interviews with four stroke survivors and 15 occupational therapists (OTs) based on real-world arm use data that we collected for contextualization. To situate our participants, we leveraged a pair of finger-worn accelerometers to collect stroke survivors' arm use data in real-world settings, which we used to create study probes for stroke survivors and OTs, respectively. The interview data was analyzed using the thematic approach. RESULTS: Our study unveiled a detailed account of (1) the receptiveness of stroke survivors and OTs for using wearable sensors in clinical practice, (2) OTs' envisioned strategies to utilize patient-generated sensor data in the light of providing patients with personalized therapy programs, and (3) practical challenges and design considerations to address for the accelerated integration of wearable systems into their practice. CONCLUSIONS: These findings offer promising directions for the design of a wearable solution that supports OTs to develop individually-tailored therapy programs for stroke survivors to improve their affected arm use.

Novel Glial Cells Missing-2 (GCM2) variants in parathyroid disorders.

OBJECTIVE: The aim of this study was to analyze variants of the gene glial cells missing-2 (GCM2), encoding a parathyroid cell-specific transcription factor, in familial hypoparathyroidism and in familial isolated hyperparathyroidism (FIHP) without and with parathyroid carcinoma. DESIGN: We characterized 2 families with hypoparathyroidism and 19 with FIHP in which we examined the mechanism of action of GCM2 variants. METHODS: Leukocyte DNA of hypoparathyroid individuals was Sanger sequenced for CASR, PTH, GNA11 and GCM2 mutations. DNA of hyperparathyroid individuals underwent MEN1, CDKN1B, CDC73, CASR, RET and GCM2 sequencing. The actions of identified GCM2 variants were evaluated by in vitro functional analyses. RESULTS: A novel homozygous p.R67C GCM2 mutation which failed to stimulate transcriptional activity in a luciferase assay was identified in affected members of two hypoparathyroid families. Oligonucleotide pull-down assay and in silico structural modeling indicated that this mutant had lost the ability to bind the consensus GCM recognition sequence of DNA. Two novel (p.I383M and p.T386S) and one previously reported (p.Y394S) heterozygous GCM2 variants that lie within a C-terminal conserved inhibitory domain were identified in three affected individuals of the hyperparathyroid families. One family member, heterozygous for p.I138M, had parathyroid carcinoma (PC), and a heterozygous p.V382M variant was found in another patient affected by sporadic PC. These variants exerted significantly enhanced in vitrotranscriptional activity, including increased stimulation of the PTH promoter. CONCLUSIONS: We provide evidence that two novel GCM2 R67C inactivating mutations with an inability to bind DNA are causative of hypoparathyroidism. Additionally, we provide evidence that two novel GCM2 variants increased transactivation of the PTH promoter in vitro and are associated with FIHP. Furthermore, our studies suggest that activating GCM2 variants may contribute to facilitating more aggressive parathyroid disease.

Use and impact of an online community for hospital patients.

OBJECTIVE: Although patient-peer support technologies have demonstrated effectiveness in a variety of health contexts-including diabetes, weight loss, and cancer-less is known about how hospitalized patients can benefit from this support. We investigated the nature of peer support in the hospital and the impact this support had on patients' hospital stays. MATERIALS AND METHODS: We created a technology, resembling an online health community, in which patients could exchange advice about their hospitalization. We deployed it at 1 pediatric hospital and 1 adult hospital. With 30 participants, we conducted bedside interviews, observed how they used the technology during their hospitalization, and completed follow-up phone interviews. RESULTS: Participants shared advice about several topics, including adjusting to the hospital and building relationships with providers. Contrary to concerns that such a system would primarily serve as a place for patients to "complain," sentiment analysis showed that 23 of 36 (64%) of the shared advice reflected positive sentiment. Patients also reported positive impacts to their quality, safety, and hospital experience due to the inpatient peer support community. DISCUSSION: Participants benefited from peer support that transcended diagnoses and individual health conditions. The shared experience of being in the hospital was sufficient to yield valuable and practical peer support. Participants who did not contribute their own advice still experienced benefits from reading their peers' advice. CONCLUSIONS: Our study demonstrated the positive nature of peer advice exchanged, and the benefits of this advice on patients' hospital stays. Inpatient peer support technologies could be an additional resource for patients to engage in their care.

Investigating data accessibility of personal health apps.

OBJECTIVE: Despite the potential values self-tracking data could offer, we have little understanding of how much access people have to "their" data. Our goal of this article is to unveil the current state of the data accessibility-the degree to which people can access their data-of personal health apps in the market. MATERIALS AND METHODS: We reviewed 240 personal health apps from the App Store and selected 45 apps that support semi-automated tracking. We characterized the data accessibility of these apps using two dimensions-data access methods and data types. RESULTS: More than 90% of our sample apps (n = 41) provide some types of data access support, which include synchronizing data with a health platform (ie, Apple Health), file download, and application program interfaces. However, the two approachable data access methods for laypeople-health platform and file download-typically put a significant limit on data format, granularity, and amount, which constrains people from easily repurposing the data. DISCUSSION: Personal data should be accessible to the people who collect them, but existing methods lack sufficient support for people in accessing the fine-grained data. Lack of standards in personal health data schema as well as frequent changes in market conditions are additional hurdles to data accessibility. CONCLUSIONS: Many stakeholders including patients, healthcare providers, researchers, third-party developers, and the general public rely on data accessibility to utilize personal data for various goals. As such, improving data accessibility should be considered as an important factor in designing personal health apps and health platforms.

Impact of Personal Health Records and Wearables on Health Outcomes and Patient Response: Three-Arm Randomized Controlled Trial.

BACKGROUND: Although using the technologies for a variety of chronic health conditions such as personal health record (PHR) is reported to be acceptable and useful, there is a lack of evidence on the associations between the use of the technologies and the change of health outcome and patients' response to a digital health app. OBJECTIVE: This study aimed to examine the impact of the use of PHR and wearables on health outcome improvement and sustained use of the health app that can be associated with patient engagement. METHODS: We developed an Android-based mobile phone app and used a wristband-type activity tracker (Samsung Charm) to collect data on health-related daily activities from individual patients. Dietary record, daily step counts, sleep log, subjective stress amount, blood pressure, and weight values were recorded. We conducted a prospective randomized clinical trial across 4 weeks on those diagnosed with obstructive sleep apnea (OSA) who had visited the outpatient clinic of Seoul National University Bundang Hospital. The trial randomly assigned 60 patients to 3 subgroups including 2 intervention groups: (1) mobile app and wearable device users (n=20), (2) mobile app-only users (n=20), and (3) controls (n=20). The primary outcome measure was weight change. Body weights before and after the trial were recorded and analyzed during clinic visits. Changes in OSA-related respiratory parameters such as respiratory disturbance, apnea-hypopnea, and oxygenation desaturation indexes and snoring comprised the secondary outcome and were analyzed for each participant. RESULTS: We collected the individual data for each group during the trial, specifically anthropometric measurement and laboratory test results for health outcomes, and the app usage logs for patient response were collected and analyzed. The body weight showed a significant reduction in the 2 intervention groups after intervention, and the mobile app-only group showed more weight loss compared with the controls (P=.01). There were no significant changes in sleep-related health outcomes. From a patient response point of view, the average daily step counts (8165 steps) from the app plus wearable group were significantly higher than those (6034 steps) from the app-only group because they collected step count data from different devices (P=.02). The average rate of data collection was not different in physical activity (P=.99), food intake (P=.98), sleep (P=.95), stress (P=.70), and weight (P=.90) in the app plus wearable and app-only groups, respectively. CONCLUSIONS: We tried to integrate PHR data that allow clinicians and patients to share lifelog data with the clinical workflow to support lifestyle interventions. Our results suggest that a PHR-based intervention may be successful in losing body weight and improvement in lifestyle behavior. TRIAL REGISTRATION: ClinicalTrials.gov NCT03200223; https://clinicaltrials.gov/ct2/show/NCT03200223 (Archived by WebCite at http://www.webcitation.org/74baZmnCX).

Effect of Lifestyle Modification Using a Smartphone Application on Obesity With Obstructive Sleep Apnea: A Short-term, Randomized Controlled Study.

OBJECTIVES: To investigate the short-term effects of a lifestyle modification intervention based on a mobile application (app) linked to a hospital electronic medical record (EMR) system on weight reduction and obstructive sleep apnea (OSA). METHODS: We prospectively enrolled adults (aged >20 years) with witnessed snoring or sleep apnea from a sleep clinic. The patients were randomized into the app user (n=24) and control (n=23) groups. The mobile app was designed to collect daily lifestyle data by wearing a wrist activity tracker and reporting dietary intake. A summary of the lifestyle data was displayed on the hospital EMR and was reviewed. In the control group, the lifestyle modification was performed as per usual practice. All participants underwent peripheral arterial tonometry (WatchPAT) and body mass index (BMI) measurements at baseline and after 4 weeks of follow-up. RESULTS: Age and BMI did not differ significantly between the two groups. While we observed a significant decrease in the BMI of both groups, the decrease was greater in the app user group (P <0.001). Apnea-hypopnea index, respiratory distress index, and oxygenation distress index did not change significantly in both groups. However, the proportion of sleep spent snoring at >45 dB was significantly improved in the app user group alone (P =0.014). In either group, among the participants with successful weight reduction, the apnea-hypopnea index was significantly reduced after 4 weeks (P =0.015). Multiple regression analyses showed that a reduction in the apnea-hypopnea index was significantly associated with BMI. CONCLUSION: Although a short-term lifestyle modification approach using a mobile app was more effective in achieving weight reduction, improvement in OSA was not so significant. Long-term efficacy of this mobile app should be evaluated in the future studies.

Networking for philanthropy: increasing volunteer behavior via social networking sites.

Social networking sites (SNSs) provide a unique social venue to engage the young generation in philanthropy through their networking capabilities. An integrated model that incorporates social capital into the Theory of Reasoned Action is developed to explain volunteer behavior through social networks. As expected, volunteer behavior was predicted by volunteer intention, which was influenced by attitudes and subjective norms. In addition, social capital, an outcome of the extensive use of SNSs, was as an important driver of users' attitude and subjective norms toward volunteering via SNSs.

Nasal augmentation using injectable alginate and mesenchymal stem cells in the rabbit.

BACKGROUND: The goal of this study was to evaluate the use of the autogenous mesenchymal stem cells (MSCs) impregnated in an injectable alginate gel containing platelet-rich plasma (PRP) for nasal augmentation in rabbit model. METHODS: Bone marrow-derived MSCs were isolated and expanded from New Zealand white rabbits. At confluence, the cells were mixed with sodium alginate solution. PRP was prepared from the rabbits and it was immediately mixed into the alginate-cell mixture. The cell-PRP-alginate mix was injected into a subcutaneous nasal area. Eight weeks after injection changes in facial contour, newly formed nasal hump was analyzed and the amount of chondroitin sulfate in tissue was measured. RESULTS: Augmented nasal dorsa maintained their original shape until harvest. Immunohistochemical staining revealed that the deposited matrix was composed of type II collagen and that it was distributed abundantly and widely in the connective tissue of the tissue generated. The amount of chondroitin sulfate (main component of the proteoglycan in cartilage) produced was significantly higher when MSCs and PRP-alginate were used. CONCLUSION: Injectable PRP-alginate gel containing autologous mesenchymal stem cells may offer a useful means of facial soft tissue augmentation.