Correction: iCHECK-DH: Guidelines and Checklist for the Reporting on Digital Health Implementations.

[This corrects the article DOI: 10.2196/46694.].

iCHECK-DH: Guidelines and Checklist for the Reporting on Digital Health Implementations.

BACKGROUND: Implementation of digital health technologies has grown rapidly, but many remain limited to pilot studies due to challenges, such as a lack of evidence or barriers to implementation. Overcoming these challenges requires learning from previous implementations and systematically documenting implementation processes to better understand the real-world impact of a technology and identify effective strategies for future implementation. OBJECTIVE: A group of global experts, facilitated by the Geneva Digital Health Hub, developed the Guidelines and Checklist for the Reporting on Digital Health Implementations (iCHECK-DH, pronounced "I checked") to improve the completeness of reporting on digital health implementations. METHODS: A guideline development group was convened to define key considerations and criteria for reporting on digital health implementations. To ensure the practicality and effectiveness of the checklist, it was pilot-tested by applying it to several real-world digital health implementations, and adjustments were made based on the feedback received. The guiding principle for the development of iCHECK-DH was to identify the minimum set of information needed to comprehensively define a digital health implementation, to support the identification of key factors for success and failure, and to enable others to replicate it in different settings. RESULTS: The result was a 20-item checklist with detailed explanations and examples in this paper. The authors anticipate that widespread adoption will standardize the quality of reporting and, indirectly, improve implementation standards and best practices. CONCLUSIONS: Guidelines for reporting on digital health implementations are important to ensure the accuracy, completeness, and consistency of reported information. This allows for meaningful comparison and evaluation of results, transparency, and accountability and informs stakeholder decision-making. i-CHECK-DH facilitates standardization of the way information is collected and reported, improving systematic documentation and knowledge transfer that can lead to the development of more effective digital health interventions and better health outcomes.

Applications of Space Technologies to Global Health: Scoping Review.

BACKGROUND: Space technology has an impact on many domains of activity on earth, including in the field of global health. With the recent adoption of the United Nations' Sustainable Development Goals that highlight the need for strengthening partnerships in different domains, it is useful to better characterize the relationship between space technology and global health. OBJECTIVE: The aim of this study was to identify the applications of space technologies to global health, the key stakeholders in the field, as well as gaps and challenges. METHODS: We used a scoping review methodology, including a literature review and the involvement of stakeholders, via a brief self-administered, open-response questionnaire. A distinct search on several search engines was conducted for each of the four key technological domains that were previously identified by the UN Office for Outer Space Affairs' Expert Group on Space and Global Health (Domain A: remote sensing; Domain B: global navigation satellite systems; Domain C: satellite communication; and Domain D: human space flight). Themes in which space technologies are of benefit to global health were extracted. Key stakeholders, as well as gaps, challenges, and perspectives were identified. RESULTS: A total of 222 sources were included for Domain A, 82 sources for Domain B, 144 sources for Domain C, and 31 sources for Domain D. A total of 3 questionnaires out of 16 sent were answered. Global navigation satellite systems and geographic information systems are used for the study and forecasting of communicable and noncommunicable diseases; satellite communication and global navigation satellite systems for disaster response; satellite communication for telemedicine and tele-education; and global navigation satellite systems for autonomy improvement, access to health care, as well as for safe and efficient transportation. Various health research and technologies developed for inhabited space flights have been adapted for terrestrial use. CONCLUSIONS: Although numerous examples of space technology applications to global health exist, improved awareness, training, and collaboration of the research community is needed.

[Moving towards patient-centered care using a mobile application : the Concerto project].

The benefits of patient empowerment are more and more recognized, and digital technologies have an important potential to favor it. The mobile application Concerto, prototyped during a hackathon, was co-created by caregivers, developers and patients by using a user-centered design and an agile development methodology. It uses the information available in the hospital information system to provide patients with an up-to-date schedule of care, targeted medical and practical information, a presentation of the care team and a tool promoting interactions with caregivers. The project is currently in experimental phase in 4 care units, and regularly improved through continuous evaluation and integration of new modules.

Les bénéfices de l'engagement des patients dans leurs soins sont de plus en plus reconnus et les technologies numériques disposent d'un potentiel important pour le favoriser. L'application mobile Concerto, prototypée lors d'un hackathon, a été cocréée par des soignants, des développeurs et des patients en utilisant une méthodologie de développement agile, basée sur les besoins utilisateurs. Elle utilise les informations présentes dans le système d'information hospitalier pour proposer au patient un agenda de soins mis à jour en temps réel, une information médicale et pratique adaptée, une présentation de l'équipe soignante et un outil de préparation aux interactions patient-soignant. Actuellement en phase pilote dans quatre unités, le projet poursuit son amélioration sur la base d'une évaluation continue et d'intégration de nouveaux modules.

Interleukin-36 potently stimulates human M2 macrophages, Langerhans cells and keratinocytes to produce pro-inflammatory cytokines.

Interleukin (IL)-36 cytokines belong to the IL-1 family and include three agonists, IL-36 α, ß and γ and one inhibitor, IL-36 receptor antagonist (IL-36Ra). IL-36 and IL-1 (α and ß) activate similar intracellular pathways via their related heterodimeric receptors, IL-36R/IL-1RAcP and IL-1R1/IL-1RAcP, respectively. However, excessive IL-36 versus IL-1 signaling induces different phenotypes in humans, which may be related to differential expression of their respective receptors. We examined the expression of IL-36R, IL-1R1 and IL-1RAcP mRNA in human peripheral blood, tonsil and skin immune cells by RT-qPCR. Monocyte-derived dendritic cells (MDDC), M0, M1 or M2-polarized macrophages, primary keratinocytes, dermal macrophages and Langerhans cells (LC) were stimulated with IL-1ß or IL-36ß. Cytokine production was assessed by RT-qPCR and immunoassays. The highest levels of IL-36R mRNA were found in skin-derived keratinocytes, LC, dermal macrophages and dermal CD1a(+) DC. In the blood and in tonsils, IL-36R mRNA was predominantly found in myeloid cells. By contrast, IL-1R1 mRNA was detected in almost all cell types with higher levels in tonsil and skin compared to peripheral blood immune cells. IL-36ß was as potent as IL-1ß in stimulating M2 macrophages, keratinocytes and LC, less potent than IL-1ß in stimulating M0 macrophages and MDDC, and exerted no effects in M1 and dermal macrophages. Levels of IL-1Ra diminished the ability of M2 macrophages to respond to IL-1. Taken together, these data are consistent with the association of excessive IL-36 signaling with an inflammatory skin phenotype and identify human LC and M2 macrophages as new IL-36 target cells.

The interleukin (IL)-1 cytokine family--Balance between agonists and antagonists in inflammatory diseases.

The interleukin (IL)-1 family of cytokines comprises 11 members, including 7 pro-inflammatory agonists (IL-1α, IL-1ß, IL-18, IL-33, IL-36α, IL-36ß, IL-36γ) and 4 defined or putative antagonists (IL-1R antagonist (IL-1Ra), IL-36Ra, IL-37, and IL-38) exerting anti-inflammatory activities. Except for IL-1Ra, IL-1 cytokines do not possess a leader sequence and are secreted via an unconventional pathway. In addition, IL-1ß and IL-18 are produced as biologically inert pro-peptides that require cleavage by caspase-1 in their N-terminal region to generate active proteins. N-terminal processing is also required for full activity of IL-36 cytokines. The IL-1 receptor (IL-1R) family comprises 10 members and includes cytokine-specific receptors, co-receptors and inhibitory receptors. The signaling IL-1Rs share a common structure with three extracellular immunoglobulin (Ig) domains and an intracellular Toll-like/IL-1R (TIR) domain. IL-1 cytokines bind to their specific receptor, which leads to the recruitment of a co-receptor and intracellular signaling. IL-1 cytokines induce potent inflammatory responses and their activity is tightly controlled at the level of production, protein processing and maturation, receptor binding and post-receptor signaling by naturally occurring inhibitors. Some of these inhibitors are IL-1 family antagonists, while others are IL-1R family members acting as membrane-bound or soluble decoy receptors. An imbalance between agonist and antagonist levels can lead to exaggerated inflammatory responses. Several genetic modifications or mutations associated with dysregulated IL-1 activity and autoinflammatory disorders were identified in mouse models and in patients. These findings paved the road to the successful use of IL-1 inhibitors in diseases that were previously considered as untreatable.

A Mobile App (Concerto) to Empower Hospitalized Patients in a Swiss University Hospital: Development, Design, and Implementation Report.

BACKGROUND: Patient empowerment can be associated with better health outcomes, especially in the management of chronic diseases. Digital health has the potential to promote patient empowerment. OBJECTIVE: Concerto is a mobile app designed to promote patient empowerment in an in-patient setting. This implementation report focuses on the lessons learned during its implementation. METHODS: The app was conceptualized and prototyped during a hackathon. Concerto uses hospital information system (HIS) data to offer the following key functionalities: a care schedule, targeted medical information, practical information, information about the on-duty care team, and a medical round preparation module. Funding was obtained following a feasibility study, and the app was developed and implemented in four pilot divisions of a Swiss University Hospital using institution-owned tablets. IMPLEMENTATION (RESULTS): The project lasted for 2 years with effective implementation in the four pilot divisions and was maintained within budget. The induced workload on caregivers impaired project sustainability and warranted a change in our implementation strategy. The presence of a killer function would have facilitated the deployment. Furthermore, our experience is in line with the well-accepted need for both high-quality user training and a suitable selection of superusers. Finally, by presenting HIS data directly to the patient, Concerto highlighted the data that are not fit for purpose and triggered data curation and standardization initiatives. CONCLUSIONS: This implementation report presents a real-world example of designing, developing, and implementing a patient-empowering mobile app in a university hospital in-patient setting with a particular focus on the lessons learned. One limitation of the study is the lack of definition of a "key success" indicator.

Grippenet: A New Tool for the Monitoring, Risk-Factor and Vaccination Coverage Analysis of Influenza-Like Illness in Switzerland.

Implemented in Switzerland in November 2016, Grippenet provides Internet-based participatory surveillance of influenza-like illness (ILI). The aim of this research is to test the feasibility of such a system and its ability to detect risk factors and to assess ILI-related behaviors. Participants filled in a web-based socio-demographic and behavioral questionnaire upon registration, and a weekly symptoms survey during the influenza season. ILI incidence was calculated weekly, and risk factors associated to ILI were analyzed at the end of each season. From November 2016 to May 2019, 1247 participants were included. The crossing of the Sentinel System (Sentinella) epidemic threshold was associated with an increase or decrease of Grippenet ILI incidence, within the same week or earlier. The number of active users varied according to ILI incidence. Factors associated with ILI were: ages 0-4 compared with 5-14 (adjusted odds ratio (AOR) 0.6, 95% confidence interval (CI) 0.19-0.99), 15-29 (AOR 0.29, 95% CI 0.15-0.60), and 65+ (AOR 0.38, 95% CI 0.16-0.93); female sex (male AOR 0.81, 95% CI 0.7-0.95); respiratory allergies (AOR 1.58, 95% CI 1.38-1.96), not being vaccinated (AOR 2.4, 95% CI 1.9-3.04); and self-employment (AOR 1.97, 95% CI 1.33-3.03). Vaccination rates were higher than those of the general population but not high enough to meet the Swiss recommendations. Approximately, 36.2% to 42.5% of users who reported one or more ILIs did not seek medical attention. These results illustrate the potential of Grippenet in complementing Sentinella for ILI monitoring in Switzerland.

Participation in lung cancer screening programs: are there gender and social differences? A systematic review.

Lung cancer remains the leading cause of cancer mortality worldwide. A number of screening trials for early detection of lung cancer exist, using chest X-ray, low-dose computed tomography, or both. However, little is known about the socio-demographic characteristics of participants in lung cancer screening programs. As gender and socio-economic determinants are important variables to consider for successful program implementation, this review aims to characterize the participants in such programs and to investigate whether differences in representation exist across screening programs. Systematic methods were used to identify relevant studies. A search was undertaken to locate all studies published up to August 2017 assessing the socio-demographic profile of participants in lung cancer screening programs. A search strategy was developed, refined, and implemented to search in two different online databases (MEDLINE and Web of Sciences). A total of 1588 references were retrieved of which 14 were eligible for review. The results highlight differences in gender and social characteristics of participants across programs, while noting that differences may be partly explained by the various epidemiological contexts, program inclusion criteria, and socio-economic status (SES) measures collected. Most importantly, despite a well-recognized predominance of low SES among heavy smokers, people with high SES are seemingly over-represented among participants. Male participants also seem to be over-represented. These findings are important to help inform the development and implementation processes of future lung cancer screening programs, which should likely include strategies for engaging women as well as individuals with low SES and, of course, those most at risk for developing lung cancer.

Research Ethics in the European Influenzanet Consortium: Scoping Review.

BACKGROUND: Influenzanet was launched in several European countries to monitor influenza-like illness during flu seasons with the help of volunteering participants and Web-based technologies. As in the case of developing fields, ethical approaches are not well developed in the collection, processing, and analysis of participants' information. Existing controversies and varying national ethical regulations can, thus, hamper efficient cross-border research collaboration to the detriment of quality disease surveillance. OBJECTIVE: This scoping review characterizes current practices on how ethical, legal, and social issues (ELSIs) pertinent to research ethics are handled by different Influenzanet country groups to analyze similarities and identify the need for further harmonization of ethical approaches. METHODS: A literature search was carried out on PubMed, Web of Science, Global Digital Library on Ethics, and Bioethics Literature Database to identify ELSIs for Influenzanet country platforms. Only English-language papers were included with publication dates from 2003 to 2017. Publications were screened for the application of bioethics principles in the implementation of country platforms. Additional publications gathered from the Influenzanet Consortium website, reference screening, and conference proceeding were screened for ELSIs. RESULTS: We gathered 96 papers from our search methodology. In total, 28 papers that mentioned ELSIs were identified and included in this study. The Research Ethics Committee (REC) approvals were sought for recruiting participants and collecting their data in 8 of 11 country platforms and informed e-consent was sought from participants in 9 of 11 country platforms. Furthermore, personal data protection was ensured throughout the Consortium using data anonymization before processing and analysis and using aggregated data. CONCLUSIONS: Epidemics forecasting activities, such as Influenzanet, are beneficial; however, its benefits could be further increased through the harmonization of data gathering and ethical requirements. This objective is achievable by the Consortium. More transparency should be promoted concerning REC-approved research for Influenzanet-like systems. The validity of informed e-consent could also be increased through the provision of a user friendly and standard information sheet across the Consortium where participants agree to its terms, conditions, and privacy policies before being able to fill in the questionnaire. This will help to build trust in the general public while preventing any decline in participation.

SIK inhibition in human myeloid cells modulates TLR and IL-1R signaling and induces an anti-inflammatory phenotype.

Macrophage polarization into a phenotype producing high levels of anti-inflammatory IL-10 and low levels of proinflammatory IL-12 and TNF-α cytokines plays a pivotal role in the resolution of inflammation. Salt-inducible kinases synergize with TLR signaling to restrict the formation of these macrophages. The expression and function of salt-inducible kinase in primary human myeloid cells are poorly characterized. Here, we demonstrated that the differentiation from peripheral blood monocytes to macrophages or dendritic cells induced a marked up-regulation of salt-inducible kinase protein expression. With the use of 2 structurally unrelated, selective salt-inducible kinase inhibitors, HG-9-91-01 and ARN-3236, we showed that salt-inducible kinase inhibition significantly decreased proinflammatory cytokines (TNF-α, IL-6, IL-1ß, and IL-12p40) and increased IL-10 secretion by human myeloid cells stimulated with TLR2 and-4 agonists. Differently than in mouse cells, salt-inducible kinase inhibition did not enhance IL-1Ra production in human macrophages. Salt-inducible kinase inhibition blocked several markers of proinflammatory (LPS + IFN-γ)-polarized macrophages [M(LPS + IFN-γ)] and induced a phenotype characterized by low TNF-α/IL-6/IL-12p70 and high IL-10. The downstream effects observed with salt-inducible kinase inhibitors on cytokine modulation correlated with direct salt-inducible kinase target (CREB-regulated transcription coactivator 3 and histone deacetylase 4) dephosphorylation in these cells. More importantly, we showed for the first time that salt-inducible kinase inhibition decreases proinflammatory cytokines in human myeloid cells upon IL-1R stimulation. Altogether, our results expand the potential therapeutic use of salt-inducible kinase inhibitors in immune-mediated inflammatory diseases.

Inflammation: IL-36 has proinflammatory effects in skin but not in joints.

Given the known involvement of IL-36 in psoriasis it might be surprising that the latest mouse models show that inhibiting IL-36 signalling does not alter the course of inflammatory arthritis. Can we now add IL-36 to the list of inflammatory mediators that are not viable DMARD targets?