Health System Stakeholders' Perspective on the Role of Mobile Health and Its Adoption in the Swiss Health System: Qualitative Study.

BACKGROUND: Digital health solutions have great potential to change the way health care is delivered, including better clinical outcomes and improved processes and access to health services. However, the adoption of mobile health (mHealth) solutions for patient monitoring has been rather slow in Switzerland. The reasons are complex, and a better understanding is needed to leverage the full potential of mHealth. OBJECTIVE: This study aimed to deepen the understanding of the potential relevance and influence of mHealth for the health system and health care provision, and factors influencing its adoption. The findings will be used to provide an outlook on feasible recommendations for action. METHODS: We conducted a qualitative survey using a maximum variation sample of a heterogeneous group of stakeholders (N=50) in the Swiss health care system with a profound knowledge of digital health and medical devices. A semistructured interview guide including open- and closed-ended questions was used to address questions around mHealth relevance and its influence on the health system, the relevance of selected determinants for mHealth adoption, and important influencing factors. A content analysis method was applied. RESULTS: Overall, respondents thought that mHealth would have a beneficial impact on the Swiss health system but that its adoption would evolve slowly. We derived 23 key opportunities regarding patient and patient pathway, treatment of disease, and diseases and health conditions. High consistency in answers among respondents was observed for treatment of disease. Stakeholders' attitudes toward mHealth adoption along the relevance of 23 preselected determinants were relatively consistent. However, we obtained diverging attitudes regarding the influence of trends, enablers, and restraints in Switzerland and translated them into 26 key themes influencing mHealth adoption. Relevant trends comprise changing needs and expectations of patients, a rising need for efficient health care delivery, growing interest in improved outpatient care, and emerging technologies and progressing digitization. Important enablers include growing demand for new financing schemes and incentive concepts, rising demand for comprehensive information on and stronger body of evidence for mHealth use cases, and increasing need for easy to use alternate care approaches. Challenging restraints are rigidness of thinking and siloed actions of health system actors, complexity of changing the existing regulations and structures, little understanding of mHealth use and the role of clinicians, and risk of further polarization of the population. CONCLUSIONS: This study provides a comprehensive look at mHealth in the Swiss health system. It becomes apparent that strong governance is inevitable to foster a sustainable data strategy and to reconcile the different interests of stakeholders. The use of mHealth will add value but will not necessarily reduce the burden on the system caused by emerging societal needs and changing disease prevalence.

Cell-free transmission of human adenovirus by passive mass transfer in cell culture simulated in a computer model.

Viruses spread between cells, tissues, and organisms by cell-free and cell-cell transmissions. Both mechanisms enhance disease development, but it is difficult to distinguish between them. Here, we analyzed the transmission mode of human adenovirus (HAdV) in monolayers of epithelial cells by wet laboratory experimentation and a computer simulation. Using live-cell fluorescence microscopy and replication-competent HAdV2 expressing green fluorescent protein, we found that the spread of infection invariably occurred after cell lysis. It was affected by convection and blocked by neutralizing antibodies but was independent of second-round infections. If cells were overlaid with agarose, convection was blocked and round plaques developed around lytic infected cells. Infected cells that did not lyse did not give rise to plaques, highlighting the importance of cell-free transmission. Key parameters for cell-free virus transmission were the time from infection to lysis, the dose of free viruses determining infection probability, and the diffusion of single HAdV particles in aqueous medium. With these parameters, we developed an in silico model using multiscale hybrid dynamics, cellular automata, and particle strength exchange. This so-called white box model is based on experimentally determined parameters and reproduces viral infection spreading as a function of the local concentration of free viruses. These analyses imply that the extent of lytic infections can be determined by either direct plaque assays or can be predicted by calculations of virus diffusion constants and modeling.

Chemotactic antiviral cytokines promote infectious apical entry of human adenovirus into polarized epithelial cells.

Mucosal epithelia provide strong barriers against pathogens. For instance, the outward facing apical membrane of polarized epithelial cells lacks receptors for agents, such as hepatitis C virus, herpesvirus, reovirus, poliovirus or adenovirus. In addition, macrophages eliminate pathogens from the luminal space. Here we show that human adenovirus type 5 engages an antiviral immune response to enter polarized epithelial cells. Blood-derived macrophages co-cultured apically on polarized epithelial cells facilitate epithelial infection. Infection also occurs in the absence of macrophages, if virus-conditioned macrophage-medium containing the chemotactic cytokine CXCL8 (interleukin-8), or recombinant CXCL8 are present. In polarized cells, CXCL8 activates a Src-family tyrosine kinase via the apical CXCR1 and CXCR2 receptors. This activation process relocates the viral co-receptor ανß3 integrin to the apical surface, and enables apical binding and infection with adenovirus depending on the primary adenovirus receptor CAR. This paradigm may explain how other mucosal pathogens enter epithelial cells.

Analysis of adenovirus trans-complementation-mediated gene expression controlled by melanoma-specific TETP promoter in vitro.

BACKGROUND: Human adenoviruses (Ads) have substantial potential for clinical applications in cancer patients. Conditionally replicating adenoviruses (CRAds) include oncolytic adenoviruses in which expression of the immediate early viral transactivator protein E1A is controlled by a cancer cell-selective promoter. To enhance efficacy, CRAds are further armed to contain therapeutic genes. Due to size constraints of the capsid geometry, the capacity for packaging transgenes into Ads is, however, limited. To overcome this limitation, the employment of E1A-deleted replication-deficient viruses carrying therapeutic genes in combination with replication-competent CRAd vectors expressing E1A in trans has been proposed. Most trans-complementing studies involved transgene expressions from strong ubiquitous promoters, and thereby relied entirely on the cancer cell specificity of the CRAd vector. RESULTS: Here we tested the trans-complementation of a CRAd and a replication-deficient transgene vector containing the same cancer cell-selective promoter. Hereto, we generated two new vectors expressing IL-2 and CD40L from a bicistronic expression cassette under the control of the melanoma/melanocyte-specific tyrosinase enhancer tyrosinase promoter (TETP), which we previously described for the melanoma-specific CRAd vector AdDeltaEP-TETP. These vectors gave rise to tightly controlled melanoma-specific transgene expression levels, which were only 5 to 40-fold lower than those from vectors controlled by the nonselective CMV promoter. Reporter analyses using Ad-CMV-eGFP in combination with AdDeltaEP-TETP revealed a high level of trans-complementation in melanoma cells (up to about 30-fold), but not in non-melanoma cells, unlike the AdCMV-eGFP/wtAd5 binary vector system, which was equally efficient in melanoma and non-melanoma cells. Similar findings were obtained when replacing the transgene vector AdCMV-eGFP with AdCMV-IL-2 or AdCMV-CD40L. However, the combination of the novel AdTETP-CD40L/IL-2 vector with AdDeltaEP-TETP or wtAd5 gave reproducible moderate 3-fold enhancements of IL-2 by trans-complementation only. CONCLUSIONS: The cancer cell-selective TETP tested here did not give the expected enforceable transgene expression typically achieved in the Ad trans-complementing system. Reasons for this could include virus-mediated down regulation of limiting transcription factors, and/or competition for such factors by different promoters. Whether this finding is unique to the particular promoter system tested here, or also occurs with other promoters warrants further investigations.