Targeting behavioral factors with digital health and shared decision-making to promote cardiac rehabilitation-a narrative review.

Cardiac rehabilitation (CR) represents an important steppingstone for many cardiac patients into a more heart-healthy lifestyle to prevent premature death and improve quality of life years. However, CR is underutilized worldwide. In order to support the development of targeted digital health interventions, this narrative review (I) provides understandings of factors influencing CR utilization from a behavioral perspective, (II) discusses the potential of digital health technologies (DHTs) to address barriers and reinforce facilitators to CR, and (III) outlines how DHTs could incorporate shared decision-making to support CR utilization. A narrative search of reviews in Web of Science and PubMed was conducted to summarize evidence on factors influencing CR utilization. The factors were grouped according to the Behaviour Change Wheel. Patients' Capability for participating in CR is influenced by their disease knowledge, awareness of the benefits of CR, information received, and interactions with healthcare professionals (HCP). The Opportunity to attend CR is impacted by healthcare system factors such as referral processes and HCPs' awareness, as well as personal resources including logistical challenges and comorbidities. Patients' Motivation to engage in CR is affected by emotions, factors such as gender, age, self-perception of fitness and control over the cardiac condition, as well as peer comparisons. Based on behavioral factors, this review identified intervention functions that could support an increase of CR uptake: Future DHTs aiming to support CR utilization may benefit from incorporating information for patients and HCP education, enabling disease management and collaboration along the patient pathway, and enhancing social support from relatives and peers. To conclude, considerations are made how future innovations could incorporate such functions.

Smartphone Apps for Food Purchase Choices: Scoping Review of Designs, Opportunities, and Challenges.

BACKGROUND: Smartphone apps can aid consumers in making healthier and more sustainable food purchases. However, there is still a limited understanding of the different app design approaches and their impact on food purchase choices. An overview of existing food purchase choice apps and an understanding of common challenges can help speed up effective future developments. OBJECTIVE: We examined the academic literature on food purchase choice apps and provided an overview of the design characteristics, opportunities, and challenges for effective implementation. Thus, we contribute to an understanding of how technologies can effectively improve food purchase choice behavior and provide recommendations for future design efforts. METHODS: Following the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines, we considered peer-reviewed literature on food purchase choice apps within IEEE Xplore, PubMed, Scopus, and ScienceDirect. We inductively coded and summarized design characteristics. Opportunities and challenges were addressed from both quantitative and qualitative perspectives. From the quantitative perspective, we coded and summarized outcomes of comparative evaluation trials. From the qualitative perspective, we performed a qualitative content analysis of commonly discussed opportunities and challenges. RESULTS: We retrieved 55 articles, identified 46 unique apps, and grouped them into 5 distinct app types. Each app type supports a specific purchase choice stage and shares a common functional design. Most apps support the product selection stage (selection apps; 27/46, 59%), commonly by scanning the barcode and displaying a nutritional rating. In total, 73% (8/11) of the evaluation trials reported significant findings and indicated the potential of food purchase choice apps to support behavior change. However, relatively few evaluations covered the selection app type, and these studies showed mixed results. We found a common opportunity in apps contributing to learning (knowledge gain), whereas infrequent engagement presents a common challenge. The latter was associated with perceived burden of use, trust, and performance as well as with learning. In addition, there were technical challenges in establishing comprehensive product information databases or achieving performance accuracy with advanced identification methods such as image recognition. CONCLUSIONS: Our findings suggest that designs of food purchase choice apps do not encourage repeated use or long-term adoption, compromising the effectiveness of behavior change through nudging. However, we found that smartphone apps can enhance learning, which plays an important role in behavior change. Compared with nudging as a mechanism for behavior change, this mechanism is less dependent on continued use. We argue that designs that optimize for learning within each interaction have a better chance of achieving behavior change. This review concludes with design recommendations, suggesting that food purchase choice app designers anticipate the possibility of early abandonment as part of their design process and design apps that optimize the learning experience.

Multicellular factor analysis of single-cell data for a tissue-centric understanding of disease.

Biomedical single-cell atlases describe disease at the cellular level. However, analysis of this data commonly focuses on cell-type-centric pairwise cross-condition comparisons, disregarding the multicellular nature of disease processes. Here, we propose multicellular factor analysis for the unsupervised analysis of samples from cross-condition single-cell atlases and the identification of multicellular programs associated with disease. Our strategy, which repurposes group factor analysis as implemented in multi-omics factor analysis, incorporates the variation of patient samples across cell-types or other tissue-centric features, such as cell compositions or spatial relationships, and enables the joint analysis of multiple patient cohorts, facilitating the integration of atlases. We applied our framework to a collection of acute and chronic human heart failure atlases and described multicellular processes of cardiac remodeling, independent to cellular compositions and their local organization, that were conserved in independent spatial and bulk transcriptomics datasets. In sum, our framework serves as an exploratory tool for unsupervised analysis of cross-condition single-cell atlases and allows for the integration of the measurements of patient cohorts across distinct data modalities.

Vaccination against Extracellular Vimentin for Treatment of Urothelial Cancer of the Bladder in Client-Owned Dogs.

It was recently shown that targeting extracellular vimentin (eVim) is safe and effective in preclinical models. Here, we report the safety and efficacy in client-owned dogs with spontaneous bladder cancer of CVx1, an iBoost technology-based vaccine targeting eVim in combination with COX-2 inhibition. This was a single-arm prospective phase 1/2 study with CVx1 in 20 client-owned dogs with spontaneous UC which involved four subcutaneous vaccinations with CVx1 at 2-week intervals for induction of antibody titers, followed by maintenance vaccinations at 2-month intervals. Additionally, daily cyclooxygenase (COX)-2 inhibition with meloxicam was given. The response was assessed by antibody titers, physical condition, abdominal ultrasound and thorax X-ray. The primary endpoints were the development of antibody titers, as well as overall survival compared to a historical control group receiving carboplatin and COX-2 inhibition with piroxicam. Kaplan-Meier survival analysis was performed. All dogs developed antibodies against eVim. Titers were adequately maintained for the duration of this study. A median overall survival of 374 days was observed, which was 196 days for the historical control group (p < 0.01). Short-term grade 1-2 toxicity at the injection site and some related systemic symptoms peri-vaccination were observed. No toxicity was observed related to the induced antibody response. A limitation of this study is the single-arm prospective setting. CVx1 plus meloxicam consistently induced efficient antibody titers, was well tolerated and showed prolonged survival. The results obtained merit further development for human clinical care.

Usability Testing of a Multi-Level Modeling Framework for Just-in-Time Adaptive Interventions (JITAIs) in Mobile Health.

The JITAI is an intervention design to support health behavior change. We designed a multi-level modeling framework for JITAIs and developed a proof-of-concept prototype (POC). This study aimed at investigating the usability of the POC by conducting two usability tests with students. We assessed the usability and the students' workload and success in completing tasks. In the second usability test, however, they faced difficulties in completing the tasks. We will work on hiding the complexity of the framework as well as improving the frontend and the instructions.

Logic Models for Evaluation of Complex Health Information Systems.

BACKGROUND: Complex health IT needs to be planned and evaluated. OBJECTIVES: To propose logic models for the evaluation of complex health IT. METHODS: Logic models describe input, activities, output, outcome, and impact. RESULTS AND CONCLUSION: This first example of a logic model for patient portals shows how health IT planning and evaluation may benefit from logic models.

Examination performance with flipped classroom as instructional strategy in the carbohydrate metabolism course unit at a Philippine medical school: Estimation of average treatment effect from observational data.

While the innovativeness of the flipped classroom (FC) approach promotes active participation and higher-order thinking among students, there are concerns about its effectiveness in terms of knowledge retention. Currently, there are no studies involving medical school biochemistry that evaluate this aspect of effectiveness. Thus, we conducted a historical control study that analyzed observational data from two freshman batches of the Doctor of Medicine program in our institution. Class 2021 (n = 250) served as the traditional lecture (TL) group while Class 2022 (n = 264) served as the FC group. Data on relevant observed covariates (age, sex, National Medical Admission Test or NMAT score, undergraduate degree) and the outcome variable (carbohydrate metabolism course unit examination percentage scores, as indicator of knowledge retention) were included in the analysis. Propensity scores were calculated using logit regression conditional on these observed covariates. Afterwards, 1:1 nearest-neighbor propensity score matching (PSM) was performed to produce an estimated average treatment effect (ATE) measure afforded by FC (as adjusted mean difference in examination scores between the two batches), balancing on the covariates. Nearest-neighbor matching using the calculated propensity scores effectively balanced the two groups (standardized bias <10%), producing 250 matched student-pairs that received either TL or FC. Following PSM, the FC group was found to have a significantly higher adjusted mean examination score compared to the TL group (adjusted mean difference = 5.62%, 95% CI: 2.54%, 8.72%; p < 0.001). Using this approach, we were able to demonstrate benefit of FC over TL in terms of knowledge retention, as reflected by the estimated ATE.

Synthesis and characterization of lipopolysaccharide (LPS) anchored polystyrene microparticles as a synthetic model system for attachment studies.

Outer membrane lipopolysaccharides (LPS) play a crucial role in determining attachment behavior and pathogenicity of bacteria. The aim of this study was to develop a simple procedure for anchoring bacterial lipopolysaccharides to polystyrene (PS) microparticles as a model system for in situ attachment studies. By using a swell-capture methodology, commercially available LPS of Pseudomonas aeruginosa (strain ATCC 27316 serotype 10.22) was anchored onto PS microparticles in a proof-of-concept study. A detailed chemical and morphological characterization has proven the success of LPS incorporation. It was shown that the coverage and structure of the LPS film was concentration dependent. The procedure can easily be adapted to LPS of other bacterial strains to generate a synthetic model toolkit for attachment studies.

Investigating shared decision-making during the use of a digital health tool for physical activity planning in cardiac rehabilitation.

Background: Shared decision making (SDM) between healthcare professionals and persons with CVD can have a positive impact on motivation, adherence, or sustainability regarding long-term goals and integration of cardiovascular disease (CVD) rehabilitation in the everyday lives of persons with CVD. SDM can foster the transition between regular heart-healthy activity at rehabilitation facilities and more independent activity at home, but it is often challenging to implement SDM given limited time and resources, e.g., in the daily practice of rehabilitation. Digital tools can help but must be appropriately tailored for situated use and user needs. Objective: We aimed to (1) describe in how far SDM is manifested in the situated context when using a digital tool developed by our group, and, based on that, (2) reflect on how digital health tools can be designed to facilitate and improve the SDM process. Methods: In the context of a field study, we investigated how SDM is already naturally applied and manifested when using a digital tool for joint physical activity planning in cardiac rehabilitation in clinical practice. In a two-week qualitative study, we collected data on expectations, experiences and interactions during the use of a digital health tool by seven persons with CVD and five healthcare professionals. Data was collected by means of observations, interviews, questionnaires and a self-reported diary, and analysed with a particular focus on episodes related to SDM. Results: We found that SDM was manifested in the situated context to limited extent. For example, we identified high improvement potential for more structured goal-setting and more explicit consideration of preferences and routines. Based on mapping our findings to temporal phases where SDM can be adopted, we highlight implications for design to further support SDM in clinical practice. We consider this as "SDM supportive design in digital health apps," suggesting for example step-by-step guidance to be used during the actual consultation. Conclusion: This study contributes to further understanding and integration of SDM in digital health tools with a focus on rehabilitation, to empower and support both persons with CVD and healthcare professionals.

Effects of Hospital Digitization on Clinical Outcomes and Patient Satisfaction: Nationwide Multiple Regression Analysis Across German Hospitals.

BACKGROUND: The adoption of health information technology (HIT) by health care providers is commonly believed to improve the quality of care. Policy makers in the United States and Germany follow this logic and deploy nationwide HIT adoption programs to fund hospital investments in digital technologies. However, scientific evidence for the beneficial effects of HIT on care quality at a national level remains mostly US based, is focused on electronic health records (EHRs), and rarely accounts for the quality of digitization from a hospital user perspective. OBJECTIVE: This study aimed to examine the effects of digitization on clinical outcomes and patient experience in German hospitals. Hence, this study adds to the small stream of literature in this field outside the United States. It goes beyond assessing the effects of mere HIT adoption and also considers user-perceived HIT value. In addition, the impact of a variety of technologies beyond EHRs was examined. METHODS: Multiple linear regression models were estimated using emergency care outcomes, elective care outcomes, and patient satisfaction as dependent variables. The adoption and user-perceived value of HIT represented key independent variables, and case volume, hospital size, ownership status, and teaching status were included as controls. Care outcomes were captured via risk-adjusted, observed-to-expected outcome ratios for patients who had stroke, myocardial infarction, or hip replacement. The German Patient Experience Questionnaire of Weisse Liste provided information on patient satisfaction. Information on the adoption and user-perceived value of 10 subdomains of HIT and EHRs was derived from the German 2020 Healthcare IT Report. RESULTS: Statistical analysis was based on an overall sample of 383 German hospitals. The analyzed data set suggested no significant effect of HIT or EHR adoption on clinical outcomes or patient satisfaction. However, a higher user-perceived value or quality of the installed tools did improve outcomes. Emergency care outcomes benefited from user-friendly overall digitization (ß=-.032; P=.04), which was especially driven by the user-friendliness of admission HIT (ß=-.023; P=.07). Elective care outcomes were positively impacted by user-friendly EHR installations (ß=-.138; P=.008). Similarly, the results suggested user-friendly, overall digitization to have a moderate positive effect on patient satisfaction (ß=-.009; P=.01). CONCLUSIONS: The results of this study suggest that hospital digitization is not an end in itself. Policy makers and hospitals are well advised to not only focus on the mere adoption of digital technologies but also continuously work toward digitization that is perceived as valuable by physicians and nurses who rely on it every day. Furthermore, hospital digitization strategies should consider that the assumed benefits of single technologies are not realized across all care domains.

Cancer Vaccination against Extracellular Vimentin Efficiently Adjuvanted with Montanide ISA 720/CpG.

Extracellular vimentin is a specific marker of the tumor vasculature, where it is secreted by tumor endothelial cells. Vaccination with a conjugate vaccine targeting extracellular vimentin was previously shown to induce a potent humoral immune response and tumor growth inhibition in mice. These data were obtained by vaccination using the toxic Freund's adjuvant (FA) and are therefore not directly translatable into the clinic. In the present study, we aimed to investigate the potential of the biodegradable Montanide ISA 720 adjuvant. We tested Montanide either alone (MN) or supplemented with CpG 1826 (MN-C). Both adjuvant compositions, as well as FA, resulted in a significant tumor growth inhibition and decreased vessel density in the B16F10 melanoma tumor model. Vaccination of mice with either FA or MN-C resulted in an equally potent humoral immune response towards vimentin, while the antibody titers obtained with MN alone were significantly lower compared to FA. Vaccination coincided with the infiltration of immune cells. The highest number of intratumoral immune cells was seen in tumors from the MN-C group. Therefore, we conclude that Montanide ISA 720 supplemented with CpG allows efficient vaccination against extracellular vimentin, which is a prerequisite for the transfer of the vaccine into the clinic.

Should App Self-Management Mean Self-Control? A Quantiative Study on App Supported Diabetes Self-Management.

Apps have been attested to empower patients regarding disease self-management through numerous studies. However, it is still unclear what factors determine the perception of patients whether an app is a useful tool for this purpose. A multiple regression model that was informed by the Technology Acceptance Model (TAM 2) was tested based on the answers of 235 app users with Diabetes type 1 or 2. The model accounted for 59.2% of the variance of the perceived degree of self-management. Factors belonging to the relevance-usefulness-quality complex as well as factors reflecting the patient's self-control were found to be significant in the model. Patient demographics, i.e. age, gender, app experience and type of Diabetes did not play any significant role. In conclusion, this study raises the question whether apps should be designed to strengthen self-management in the sense of self-control (e.g. own measurements, diary) as opposed to guiding and advice giving.

Effectiveness of osteopathic manipulative treatment for pediatric conditions: A systematic review.

BACKGROUND: Osteopathic manipulative treatment (OMT) is commonly used by osteopaths and osteopathic physicians to manage a large variety of pediatric complaints. OBJECTIVE: The current study reviewed the literature to determine the effectiveness of OMT for all pediatric complaints. METHODS: A systematic literature search for randomized controlled trials (RCTs) unrestricted by language or publication status was performed in July 2020 in electronic and ongoing trials databases. Included studies were assessed using the Cochrane Risk of Bias (RoB) instrument. Mean difference or standard mean difference and overall effect size were calculated. Data were synthesized using the GRADE approach. RESULTS: Forty-seven RCTs examining 37 pediatric conditions were reviewed. Twenty-three studies reported significant favorable outcomes for OMT relative to the control intervention, and 14 additional studies reported non-significant outcomes, which suggested potential favorable effects of OMT. Fifteen of the studies were judged to have a low RoB, 12 had high risk, and the remainder had unclear RoB. Using GRADE, there was moderate evidence for the effectiveness of OMT for 13 of the 43 comparisons, particularly for length of hospital stay for preterm infants, but no high-quality evidence for any condition. CONCLUSIONS: Although a number of studies indicated positive results with use of OMT, few pediatric conditions have been investigated in more than one study, which results in no high-quality evidence for any condition. Additional research may change estimates of effect, and larger, high-quality RCTs focusing on a smaller range of conditions are recommended. SYSTEMATIC REVIEW REGISTRATION: PROSPERO ID: CRD42020162479.

Research on Digital Technology Use in Cardiology: Bibliometric Analysis.

BACKGROUND: Digital technology uses in cardiology have become a popular research focus in recent years. However, there has been no published bibliometric report that analyzed the corresponding academic literature in order to derive key publishing trends and characteristics of this scientific area. OBJECTIVE: We used a bibliometric approach to identify and analyze the academic literature on digital technology uses in cardiology, and to unveil popular research topics, key authors, institutions, countries, and journals. We further captured the cardiovascular conditions and diagnostic tools most commonly investigated within this field. METHODS: The Web of Science electronic database was queried to identify relevant papers on digital technology uses in cardiology. Publication and citation data were acquired directly from the database. Complete bibliographic data were exported to VOSviewer, a dedicated bibliometric software package, and related to the semantic content of titles, abstracts, and keywords. A term map was constructed for findings visualization. RESULTS: The analysis was based on data from 12,529 papers. Of the top 5 most productive institutions, 4 were based in the United States. The United States was the most productive country (4224/12,529, 33.7%), followed by United Kingdom (1136/12,529, 9.1%), Germany (1067/12,529, 8.5%), China (682/12,529, 5.4%), and Italy (622/12,529, 5.0%). Cardiovascular diseases that had been frequently investigated included hypertension (152/12,529, 1.2%), atrial fibrillation (122/12,529, 1.0%), atherosclerosis (116/12,529, 0.9%), heart failure (106/12,529, 0.8%), and arterial stiffness (80/12,529, 0.6%). Recurring modalities were electrocardiography (170/12,529, 1.4%), angiography (127/12,529, 1.0%), echocardiography (127/12,529, 1.0%), digital subtraction angiography (111/12,529, 0.9%), and photoplethysmography (80/12,529, 0.6%). For a literature subset on smartphone apps and wearable devices, the Journal of Medical Internet Research (20/632, 3.2%) and other JMIR portfolio journals (51/632, 8.0%) were the major publishing venues. CONCLUSIONS: Digital technology uses in cardiology target physicians, patients, and the general public. Their functions range from assisting diagnosis, recording cardiovascular parameters, and patient education, to teaching laypersons about cardiopulmonary resuscitation. This field already has had a great impact in health care, and we anticipate continued growth.

Towards Adaptability of Just-in-Time Adaptive Interventions.

Just-in-time adaptive interventions (JITAIs) can promote behavior change in patients. It was the aim of our study to make JITAIs adaptable, i.e., to configure JITAIs for different purposes and to personalize them for different participants, whilst enabling central maintenance and integrated data analysis across deployments and individuals. We present a concept for adaptable JITAIs that was created following a design science approach. It builds on multi-level conceptual modeling and knowledge graphs and will be evaluated in user studies.

B cells, BAFF and interferons in MIS-C

Multisystem Inflammatory Syndrome in Children associated with COVID-19 (MIS-C) is a late complication of pediatric COVID-19, which follows weeks after original SARS-CoV-2 infection, regardless of its severity. It is characterized by hyperinflammation, neutrophilia, lymphopenia and activation of T cells with elevated IFN-{gamma}. Observing production of autoantibodies and parallels with systemic autoimmune disorders, such as systemic lupus erythematodes (SLE), we explored B cell phenotype and serum levels of type I, II and III interferons, as well as the cytokines BAFF and APRIL in a cohort of MIS-C patients and healthy children after COVID-19. We documented a significant elevation of IFN-{gamma}, but not IFN- and IFN-{lambda} in MIS-C patients. BAFF was elevated in MIS-C patient sera and accompanied by decreased BAFFR expression on all B cell subtypes. The proportion of plasmablasts was significantly lower in patients compared to healthy post-COVID children. We noted the presence of ENA Ro60 autoantibodies in 4/35 tested MIS-C patients. Our work shows the involvement of humoral immunity in MIS-C and hints at parallels with the pathophysiology of SLE, with autoreactive B cells driven towards autoantibody production by elevated BAFF. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=175 SRC="FIGDIR/small/22275245v1_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@166327dorg.highwire.dtl.DTLVardef@7cde7forg.highwire.dtl.DTLVardef@1f3a3b2org.highwire.dtl.DTLVardef@803175_HPS_FORMAT_FIGEXP M_FIG C_FIG Summary sentenceElevated serum BAFF in children with MIS-C supports the state of polyclonal B cell activation and autoimmune phenomena characterizing this disease.