Early prediction of platelet recovery with immature platelet fraction in patients receiving hematopoietic stem cell transplantation.

Hematopoietic stem cell transplantation (HSCT) is pivotal in treating hematologic disorders, yet it poses the risk of post-transplantation pancytopenia. Prophylactic platelet transfusions are often administered to mitigate this risk. Utilizing practical markers, such as immature platelet fraction (IPF), to predict hematopoietic recovery in advance could reduce unnecessary prophylactic transfusions. Our prospective study, involving 53 HSCT patients at Taipei Veterans General Hospital between September 2022 and May 2023, utilized the Sysmex XN analyzer to assess peripheral blood cell parameters. We investigated whether IPF could predict platelet recovery early, determined the optimal cut-off value, and compared platelet usage. Neutrophil and platelet engraftment occurred 10 (median; range: 10-12) and 15 (median; range: 15-18) days post-HSCT. Notably, 71.7% of patients exhibited an IPF increase exceeding 2% before platelet recovery. The optimal cut-off IPF on day 10 for predicting platelet recovery within five days was 2.15% (specificity 0.89, sensitivity 0.65). On average, patients received 3.89 units of post-transplantation platelet transfusion. Our results indicate that IPF serves as a predictive marker for platelet engraftment, peaking before the increase in platelet count. This insight aids clinicians in assessing the need for prophylactic platelet transfusions. Integrating reference IPF values alongside platelet counts enhances the accuracy of evaluating a patient's hematopoietic recovery status. Anticipating the timing of platelet recovery optimizes blood product usage and mitigates transfusion reaction risks.

Exploring Nurse Use of Digital Nursing Technology.

Technological developments and nursing shortages have become global trends. To solve the problem of shortage of healthcare professionals, technology may be used as a backup. Nurses constitute the largest working group in the healthcare system. Therefore, nurses are very important to the success of implementing digitization in hospitals. This cross-sectional study used the characteristics and adoption roles of innovation diffusion theory to understand technology use within the organization. Data were collected through structured questionnaires and open-ended questions from March 21 to May 31, 2022, in two hospitals in Taiwan. In total, 159 nurses agreed to participate in the study. The results of this study revealed that observability, simplicity, advantage, trialability, and compatibility positively improved the acceptance of digital nursing technology. In the distribution of users' innovative roles, early adopters had a significant impact on innovation characteristics and technology acceptance. Nurses in acute and critical care units perceived a greater comparative advantage and trial availability of digital nursing technology use than did those in general wards and outpatient clinics. In addition, based on user opinions and suggestions, the development of smart healthcare and the use of digital technology are expected to improve the quality of nursing care.

Risk factors of early disease progression and decreased survival for multiple myeloma patients after upfront autologous stem cell transplantation.

Multiple myeloma (MM) stands as the second most prevalent hematological malignancy, constituting approximately 10% of all hematological malignancies. Current guidelines recommend upfront autologous stem cell transplantation (ASCT) for transplant-eligible MM patients. This study seeks to delineate factors influencing post-ASCT outcomes in MM patients. Our cohort comprised 150 MM patients from Taipei Veterans General Hospital, with progression-free survival (PFS) as the primary endpoint and overall survival (OS) as the secondary endpoint. A Cox proportional hazards model was employed to discern potential predictive factors for survival. ASCT age ≥ 65 (hazard ratio [HR] 1.94, 95% confidence interval [CI] 1.08-3.47) and the presence of extramedullary disease (HR 2.53, 95% CI 1.53-4.19) negatively impacted PFS. Conversely, treatment response ≥ VGPR before ASCT (HR 0.52, 95% CI 0.31-0.87) and total CD34+ cells collected ≥ 4 × 106 cells/kg on the first stem cell harvesting (HR 0.52, 95% CI 0.32-0.87) were positively associated with PFS. For OS, patients with ISS stage III (HR 2.06, 95% CI 1.05-4.04), the presence of extramedullary disease (HR 3.92, 95% CI 2.03-7.58), light chain ratio ≥ 100 before ASCT (HR 7.08, 95% CI 1.45-34.59), post-ASCT cytomegalovirus infection (HR 9.43, 95% CI 3.09-28.84), and a lower conditioning melphalan dose (< 140 mg/m2; HR 2.75, 95% CI 1.23-6.17) experienced shorter OS. In contrast, post-ASCT day + 15 absolute monocyte counts (D15 AMC) > 500/µl (HR 0.36, 95% CI 0.17-0.79) and post-ASCT day + 15 platelet counts (D15 PLT) > 80,000/µl (HR 0.48, 95% CI 0.24-0.94) were correlated with improved OS. Significantly, early PLT and AMC recovery on day + 15 predicting longer OS represents a novel finding not previously reported. Other factors also align with previous studies. Our study provides real-world insights for post-ASCT outcome prediction beyond clinical trials.

Comparing transfusion reactions between pre-storage and post-storage leukoreduced apheresis platelets: an analysis using propensity score matching.

Transfusion reactions induced by platelet transfusions may be reduced and alleviated by leukocyte reduction of platelets. Although leukoreduction of apheresis platelets can be performed either pre-storage or post-storage, seldom studies directly compare the incidence of transfusion reaction in these two different blood products. We conducted a retrospective study to compare the transfusion reactions between pre-storage and post-storage leukoreduced apheresis platelets. We reviewed the general characteristics and the transfusion reactions, symptoms, and categories for inpatients who received pre-storage or post-storage leukoreduced apheresis platelets. Propensity-score matching was performed to adjust for baseline differences between groups. A total of 40,837 leukoreduction apheresis platelet orders were reviewed. 116 (0.53%) transfusion reactions were reported in 21,884 transfusions with pre-storage leukoreduction, and 174 (0.91%) reactions were reported in 18,953 transfusions with post-storage leukoreduction. Before propensity-score matching, the odds ratio for transfusion reactions in the pre-storage group relative to the post-storage group was 0.57 (95% confidence interval [CI] 0.45-0.72, P < 0.01); the odds ratio after matching was 0.63 (95% CI 0.49-0.80, P < 0.01). A two-proportion z-test revealed pre-storage leukoreduction significantly decreases the symptoms of chills, fever, itching, urticaria, dyspnea, and hypertension as compared with those in post-storage leukoreduction. Pre-storage leukoreduced apheresis platelet significantly decreased febrile non-hemolytic transfusion reaction as compared with post-storage groups. This study suggests pre-storage leukoreduction apheresis platelet significantly decreases the transfusion reaction as compared with those in post-storage leukoreduction.

Exploring Nurse' Use of Digital Nursing Technology.

This is a quantitative cross-sectional study using the characteristics of innovation diffusion theory to evaluate nurse' acceptance and adoption of digital nursing technology (DNT). Data were collected through questionnaires based on innovation diffusion theory in the wards of a regional hospital in Taiwan from March 21 to May 31, 2022. Results indicated that the higher the innovative characteristics of DNT, the higher the DNT acceptance. Difficulties with network connections contributed to negative experiences and led to recommendations for future system improvement.

Detection of cellular traction forces via the force-triggered Cas12a-mediated catalytic cleavage of a fluorogenic reporter strand.

Molecular forces generated by cell receptors are infrequent and transient, and hence difficult to detect. Here we report an assay that leverages the CRISPR-associated protein 12a (Cas12a) to amplify the detection of cellular traction forces generated by as few as 50 adherent cells. The assay involves the immobilization of a DNA duplex modified with a ligand specific for a cell receptor. Traction forces of tens of piconewtons trigger the dehybridization of the duplex, exposing a cryptic Cas12-activating strand that sets off the indiscriminate Cas12-mediated cleavage of a fluorogenic reporter strand. We used the assay to perform hundreds of force measurements using human platelets from a single blood draw to extract individualized dose-response curves and half-maximal inhibitory concentrations for a panel of antiplatelet drugs. For seven patients who had undergone cardiopulmonary bypass, platelet dysfunction strongly correlated with the need for platelet transfusion to limit bleeding. The Cas12a-mediated detection of cellular traction forces may be used to assess cell state, and to screen for genes, cell-adhesion ligands, drugs or metabolites that modulate cell mechanics.

Molecular mechanocytometry using tension-activated cell tagging.

Flow cytometry is used routinely to measure single-cell gene expression by staining cells with fluorescent antibodies and nucleic acids. Here, we present tension-activated cell tagging (TaCT) to label cells fluorescently based on the magnitude of molecular force transmitted through cell adhesion receptors. As a proof-of-concept, we analyzed fibroblasts and mouse platelets after TaCT using conventional flow cytometry.

Rapid adaptive and acute stimulatory responses to low salinity stress in Pacific white shrimp (Litopenaeus vannamei): Insights from integrative transcriptomic and proteomic analysis.

The Pacific white shrimp (Litopenaeus vannamei) is a euryhaline crustacean capable of tolerating a wide range of ambient salinity, but the strategies of hepatopancreas to rapid adaptive or acute stimulatory responses to extremely low salinity fluctuations remains unclear. In this study, we integrated transcriptomic and proteomic analyses on the hepatopancreas derived from rapid adaptative (RA) and acute stimulatory (AS) responses to extremely low salinity stress (0.3 ppt) to unveil specific regulatory mechanisms. The RA group displayed normal epithelial cells and tubule structures, while the AS group showed histological changes and lesions. A total of 754 and 649 differentially expressed genes (DEGs) were identified in RA and AS treatments, respectively. For proteome, a total of 206 and 66 differentially expressed proteins (DEPs) were obtained in the RA/CT and AS/CT comparison groups, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were conducted among the DEGs and DEPs, revealing that metabolic related pathways were significantly enriched pathways in both comparison groups. In addition, correlation analysis of transcriptomic and proteomic results showed that 20 and 3 pairs of DEGs/DEPs were identified in RA vs. CT and AS vs. CT comparison groups, respectively. This study is the first report on the rapid adaptive and acute stimulatory transcriptomic and proteomic responses of L. vannamei to extremely low salinity, shedding light on the mechanisms underlying osmoregulation in euryhaline crustaceans.

Risk Factors and Outcomes of Stem Cell Mobilization Failure in Multiple Myeloma Patients.

Introduction: Autologous hematopoietic stem cell transplantation (ASCT) is a well-established treatment for patients with multiple myeloma (MM), and adequate stem cell collection must be assured before ASCT. However, prediction of poor mobilizers (PMs) is still difficult despite several risk factors for mobilization failure having been identified. Methods: We retrospectively analyzed MM patients at Taipei Veterans General Hospital in Taiwan who underwent stem cell collection between October 2006 and August 2020. A CD34+ cell collection of <1 × 106 cells/kg was defined as a mobilization failure. The primary endpoint was mobilization failure. The secondary endpoint was overall survival (OS). Odds ratios (ORs) and 95% confidence intervals (CIs) for mobilization failure were calculated using a logistic regression model. The cumulative incidence of mortality was estimated using the Kaplan-Meier method. Results: In the multivariate analysis, absolute monocyte count <500/µL (adjusted OR 10.75, 95% CI: 1.82-63.57, p = 0.009), platelet count <150,000/µL (adjusted OR 12.49, 95% CI: 2.65-58.89, p = 0.001) before mobilization, and time interval from diagnosis to stem cell harvest ≥180 days (adjusted OR 7.69, 95% CI: 1.61-36.87, p = 0.011) were risk factors for PMs. PM patients had poorer OS compared to patients with successful stem cell collection in the univariate analysis (log-rank test p = 0.027). The predicted probability of PMs was estimated by the multiple logistic regression model with a sensitivity of 84.6% and a specificity of 84.0%. Conclusion: Absolute monocyte count <500/µL, platelet count <150,000/µL, and treatment duration more than 180 days before stem cell mobilization are risk factors for unsuccessful stem cell collection. Our prediction models have high sensitivity and specificity for mobilization failure prediction and allow for early interventions for possible PMs.

Autoinhibitory module underlies species difference in shear activation of von Willebrand factor.

BACKGROUND: Von Willebrand factor (VWF) is a multimeric plasma protein that bridges the gap between vessel injury and platelet capture at high shear rates. Under high shear or tension, VWF can become activated upon the unfolding of its autoinhibitory module (AIM). AIM unfolding exposes the A1 domain, allowing for binding to platelet glycoprotein (GP)Ibα to initiate primary hemostasis. The characteristics of the AIM and its inhibitory properties within mouse VWF are unknown. OBJECTIVES: To determine and characterize the autoinhibitory properties of mouse VWF. METHODS: Recombinant mouse VWF A1 fragments containing or lacking the flanking regions around the A1 domain were generated. We tested the ability of these fragments to bind to human or mouse GPIbα and platelets. We compared the unfolding of mouse AIM-A1 to human AIM-A1 by single-molecule force spectroscopy. RESULTS: Recombinant mouse AIM-A1 binds with higher affinity to GPIbα than its human counterpart. Recombinant mouse proteins lacking part of the AIM show increased binding to GPIbα. Activated A1 fragments lacking the AIM can effectively agglutinate platelets across the species barrier. Using single-molecule force spectroscopy, we determined that the mouse AIM unfolds under forces similar to the human AIM. Additionally, the human AIM paired with mouse A1 largely recapitulates the behavior of human AIM-A1. CONCLUSIONS: Our results suggest that the regulation of VWF-GPIbα binding has been specifically tuned to work optimally in different rheological architectures. Differences in the AIM sequence may contribute to the difference in VWF shear response between human and mice.

The Mediating Role of Psychological Well-Being in the Relationship between Self-Care Knowledge and Disease Self-Management in Patients with Hypertensive Nephropathy.

OBJECTIVE: This study aimed to investigate the correlation between self-care knowledge, psychological well-being, and disease self-management in patients with hypertensive nephropathy, and to assess the effect of psychological well-being as a mediator of self-care knowledge and disease self-management. METHODS: This is a cross-sectional study. The 220 patients with hypertensive nephropathy were recruited from a teaching hospital in Taiwan using purposive sampling. The average age was 70.14 (SD = 11.96) years old. Among them, 128 (58.2%) were male and 92 (41.8%) were female. Instruments included a hypertensive nephropathy self-care knowledge scale, the World Health Organization-5 Well-Being Index, and the chronic kidney disease self-management instrument. The mediating effect was determined with linear regression models and the Sobel test. RESULTS: The total explanatory variation of age, systolic blood pressure, psychological well-being, and self-care knowledge on the disease self-management was 27.7%. Psychological well-being was the most important explanatory factor and alone explains 16%. Psychological well-being was a partial mediator of self-care knowledge and quality of life in patients with hypertensive nephropathy, with a total effect of 23.2%. CONCLUSIONS: This study showed that older patients with hypertensive nephropathy and those with a higher systolic blood pressure had lower levels of disease self-management. The higher the patients' self-care knowledge and psychological well-being, the better their disease self-management.

Fast clearance of platelets in a commonly used mouse model for GPIbα is impeded by an anti-GPIbß antibody derivative.

BACKGROUND: Glycoprotein (GP)Ibα plays a critical role in regulating platelet clearance. Recently, we identified the mechanosensory domain (MSD) in GPIbα and reported evidence to suggest that unfolding of the GPIbα MSD induces exposure of the Trigger sequence therein and subsequent GPIb-IX signaling that accelerates platelet clearance. In a commonly used transgenic mouse model, IL4R-IbαTg, where the Trigger sequence is constitutively exposed, constitutive GPIb-IX-mediated cellular signals are present. Clearance of their platelets is also significantly faster than that of wild-type mice. Previously, an anti-GPIbß antibody RAM.1 was developed. RAM.1 inhibits GPIbα-dependent platelet signaling and activation. Further, RAM.1 also inhibits anti-GPIbα antibody-mediated filopodia formation. OBJECTIVE: To investigate whether RAM.1 can ameliorate trigger sequence exposure-mediated platelet clearance. METHODS: Spontaneous filopodia were measured by confocal microscopy. Other platelet signaling events were measured by flow cytometry. Endogenous platelet life span was tracked by Alexa 488-labeled anti-mouse GPIX antibody. RESULT: Transfected Chinese hamster ovary cells stably expressing the same chimeric IL4R-Ibα protein complex as in IL4R-IbαTg mice also constitutively exhibit filopodia, and that such filopodia could be abolished by treatment of RAM.1. Further, transfusion of a recombinant RAM.1 derivative that is devoid of its Fc portion significantly extends the endogenous life span of IL4R-IbαTg platelets. CONCLUSION: These results provide the key evidence supporting the causative link of Trigger sequence exposure to accelerated platelet clearance, and suggest that a RAM.1 derivative may be therapeutically developed to treat GPIb-IX-mediated thrombocytopenia.

The TVGH-NYCU Thal-Classifier: Development of a Machine-Learning Classifier for Differentiating Thalassemia and Non-Thalassemia Patients.

Thalassemia and iron deficiency are the most common etiologies for microcytic anemia and there are indices discriminating both from common laboratory simple automatic counters. In this study a new classifier for discriminating thalassemia and non-thalassemia microcytic anemia was generated via combination of exciting indices with machine-learning techniques. A total of 350 Taiwanese adult patients whose anemia diagnosis, complete blood cell counts, and hemoglobin gene profiles were retrospectively reviewed. Thirteen prior established indices were applied to current cohort and the sensitivity, specificity, positive and negative predictive values were calculated. A support vector machine (SVM) with Monte-Carlo cross-validation procedure was adopted to generate the classifier. The performance of our classifier was compared with original indices by calculating the average classification error rate and area under the curve (AUC) for the sampled datasets. The performance of this SVM model showed average AUC of 0.76 and average error rate of 0.26, which surpassed all other indices. In conclusion, we developed a convenient tool for primary-care physicians when deferential diagnosis contains thalassemia for the Taiwanese adult population. This approach needs to be validated in other studies or bigger database.

Turn-key mapping of cell receptor force orientation and magnitude using a commercial structured illumination microscope.

Many cellular processes, including cell division, development, and cell migration require spatially and temporally coordinated forces transduced by cell-surface receptors. Nucleic acid-based molecular tension probes allow one to visualize the piconewton (pN) forces applied by these receptors. Building on this technology, we recently developed molecular force microscopy (MFM) which uses fluorescence polarization to map receptor force orientation with diffraction-limited resolution (~250 nm). Here, we show that structured illumination microscopy (SIM), a super-resolution technique, can be used to perform super-resolution MFM. Using SIM-MFM, we generate the highest resolution maps of both the magnitude and orientation of the pN traction forces applied by cells. We apply SIM-MFM to map platelet and fibroblast integrin forces, as well as T cell receptor forces. Using SIM-MFM, we show that platelet traction force alignment occurs on a longer timescale than adhesion. Importantly, SIM-MFM can be implemented on any standard SIM microscope without hardware modifications.

DNA-Based Microparticle Tension Sensors (µTS) for Measuring Cell Mechanics in Non-planar Geometries and for High-Throughput Quantification.

Mechanotransduction, the interplay between physical and chemical signaling, plays vital roles in many biological processes. The state-of-the-art techniques to quantify cell forces employ deformable polymer films or molecular probes tethered to glass substrates. However, the applications of these assays in fundamental and clinical research are restricted by the planar geometry and low throughput of microscopy readout. Herein, we develop a DNA-based microparticle tension sensor, which features a spherical surface and thus allows for investigation of mechanotransduction at curved interfaces. The micron-scale of µTS enables flow cytometry readout, which is rapid and high throughput. We applied the method to map and measure T-cell receptor forces and platelet integrin forces at 12 and 56 pN thresholds. Furthermore, we quantified the inhibition efficiency of two anti-platelet drugs providing a proof-of-concept demonstration of µTS to screen drugs that modulate cellular mechanics.

Psychometric testing of the hemodialysis self-management instrument (HDSMI-18): A confirmatory factor analysis.

AIM: The aim of this study was to probe the rigorousness of the factor structure of the HDSMI and to test the instrument's construct validity. DESIGN: Cross-sectional study. METHODS: The hemodialysis unit of four hospitals in Taiwan provided data from 628 patients with end-stage renal disease (ESRD), through the period of September to December in 2012. The patients were divided into a calibration sample for CFA and model modification, and a validation sample for cross-validation of the postmodification model. Goodness of fit was tested with standard fit indices. RESULTS: The four latent variables (i.e. partnership, self-care, problem-solving and emotional management) were verified as dimensions of HDSMI through CFA. The construct validity of the HDSMI was improved by omitting two items, allowing one inter-item correlation and transferring the loading of one item. These modifications improved fit indices of the calibration sample. Cross-validation of the validation sample verified the construct validity of the modified HDSMI-18.

Differential regulation of the platelet GPIb-IX complex by anti-GPIbß antibodies.

BACKGROUND: Platelets' initial recognition of endothelial damage proceeds through the interaction between collagen, plasma von Willebrand factor (VWF), and the platelet glycoprotein (GP)Ib-IX complex (CD42). The GPIb-IX complex consists of one GPIbα, one GPIX, and two GPIbß subunits. Once platelets are immobilized to the subendothelial matrix, shear generated by blood flow unfolds a membrane-proximal mechanosensory domain (MSD) in GPIbα, exposing a conserved trigger sequence and activating the receptor. Currently, GPIbα appears to solely facilitate ligand-induced activation because it contains both the MSD and the binding sites for all known ligands to GPIb-IX. Despite being positioned directly adjacent to the MSD, the roles of GPIbß and GPIX in signal transduction remain murky. OBJECTIVES: To characterize a novel rat monoclonal antibody 3G6 that binds GPIbß. METHODS: Effects of 3G6 on activation of GPIb-IX are characterized in platelets and Chinese hamster ovary cells expressing GPIb-IX (CHO-Ib-IX) and compared with those of an inhibitory anti-GPIbß antibody, RAM.1. RESULTS: Both RAM.1 and 3G6 bind to purified GPIbß and GPIb-IX with high affinity. 3G6 potentiates GPIb-IX-associated filopodia formation in platelets or CHO-Ib-IX when they adhere VWF or antibodies against the ligand-binding domain (LBD) of GPIbα. Pretreatment with 3G6 also increased anti-LBD antibody-induced GPIb-IX activation. Conversely, RAM.1 inhibits nearly all GPIb-IX-related signaling in platelets and CHO-Ib-IX cells. CONCLUSIONS: These data represent the first report of a positive modulator of GPIb-IX activation. The divergent modulatory effects of 3G6 and RAM.1, both targeting GPIbß, strongly suggest that changes in the conformation of GPIbß underlie outside-in activation via GPIb-IX.

A preliminary study on the effects of the Peer-Led Self-Management (PLSM) program on self-efficacy, self-management, and physiological measures in older adults with diabetes: A block randomized controlled trial.

This study explored the effects and feasibility of the peer-led self-management (PLSM) program for older adults with diabetes. Twenty-eight participants from 10 communities in southern Taiwan were randomly allocated to experimental and control groups. Those in the experimental group were enrolled in a 4-week PLSM program; those in the control group received a self-management manual and continued their usual clinical care. Improvement in outcomes (self-efficacy, self-management, physiological measures) over time in both groups were evaluated. After PLSM intervention, self-efficacy and self-management had improved; body weight and body mass index measures of the experimental group at post-test 1 and post-test 2 were significantly lower than those of the control group (p < .001); HbA1c, total cholesterol, and triglycerides at post-test 2 were also significantly better (p < .001; p = .03; p = .02). We discuss preliminary benefits and feasibility of the PLSM program.

A Theory-Based Self-Management Training Program for Older Adult Peer Leaders with Diabetes: A Feasibility Assessment.

OBJECTIVE: To improve the quality of peer leader training, this study developed a theory-based self-management training program for older adult peer leaders with diabetes and assessed its feasibility. BACKGROUND: Current self-management programs are designed mainly to be implemented by healthcare professionals, but healthcare staff may not fully perceive the needs and obstacles of older adults in disease management due to a lack of similar illness experience. To target this problem, peer leaders with successful self-management experiences, similar cultural backgrounds and languages, and related illness experiences are trained to guide and mentor peer patients in self-management programs. STUDY DESIGN AND METHODS: This study was conducted in two stages. In stage 1, a peer leader training program was developed based on experiential learning theory as the framework and self-regulation theory as the activity design strategy. In stage 2, program feasibility was assessed via participants' feedback toward the training program by three indicators: attendance, future willingness to lead the peer-led self-management program, and leadership skills evaluated by a peer leader training assessment tool. RESULTS: In this study, peer leaders demonstrated good leadership skills by expressing active willingness to lead self-management programs in the community. Peer leaders' feedback indicated that the program's training content was helpful in preparing peer leaders to guide older adults in learning self-management skills and in improving the abilities and confidence of peer leaders in mentoring self-management. CONCLUSION: Findings in this study showed that peer leader training can impact the effectiveness and success of self-management in older adults with diabetes. Even in a small-scale study, the impact was evident, which demonstrated the feasibility of the program. More large-scale studies on the effectiveness of various peer leader training programs in diverse disciplines are recommended. CLINICAL TRIALS REGISTRY: ClinicalTrials.gov Identifier: NCT04298424 (the Peer-Led Self-Management Program).