ABSTRACT
BACKGROUND: Health care systems worldwide are struggling to keep rising costs at bay with only modest outcome improvement among many diseases. Digitization with technologies like Artificial Intelligence or Machine Learning algorithms might address this. Although digital technologies have been successfully applied in clinical studies the effect on the overall health care system so far was limited. The regulatory ecosystem or data privacy might be responsible, but other reasons may also predominate. OBJECTIVE: We analyzed how the digitization of the German health care market is currently perceived among different stakeholders and investigated reasons for its slow adaption. METHODS: This was a mixed methods study split into a qualitative Part A using the conceptual approach of the Grounded Theory and a quantitative Part B using the Delphi method. For Part A we interviewed experts in the health care system and converted the results into 17 hypotheses. The Delphi method consisted of an online survey which was sent to the participants via email and was available for three months. For the assessment of the 17 hypotheses, the participants were given a six-point Likert scale. The participants were grouped into patients, physicians, and providers of services within the German health care market. RESULTS: There was a strong alignment of opinions on the hypotheses between experts (N=21) and survey participants (N=733), with 70.5% overall agreement on 12/17 hypotheses. Physicians demonstrated the lowest level of agreement with the expert panel at 88% (15/17) disagreement, with the hypotheses "H8: Digitization in the health care system will free up jobs," and "H6: Digitization in the health care system will empower the patients," perceived to be in profound disagreement (P=.036 and P<.001, respectively). CONCLUSIONS: Despite the firm agreement among participants and experts regarding the impact of digitization on the health care system, physicians demonstrated a more negative attitude. We assume that this might be a factor contributing to the slow adoption of digitization in practice. Physicians might be struggling with changing power structures, so future measures to transform the market should involve them to a larger degree.
ABSTRACT
BACKGROUND: An adverse intrauterine environment leads to permanent physiological changes including vascular tone regulation, potentially influencing the risk for adult vascular diseases. We therefore aimed to monitor responsive NOS3 expression in human umbilical artery endothelial cells (HUAEC) and to study the underlying epigenetic signatures involved in its regulation. RESULTS: NOS3 and STAT3 mRNA levels were elevated in HUAEC of patients who suffered from placental insufficiency. 5-hydroxymethylcytosine, H3K9ac and Histone 2A (H2A).Zac at the NOS3 transcription start site directly correlated with NOS3 mRNA levels. Concomitantly, we observed entangled histone acetylation patterns and NOS3 response upon hypoxic conditions in vitro. Knock-down of either NOS3 or STAT3 by RNAi provided evidence for a functional NOS3/STAT3 relationship. Moreover, we recognized massive turnover of Stat3 at a discrete binding site in the NOS3 promoter. Interestingly, induced hyperacetylation resulted in short-termed increase of NOS3 mRNA followed by deferred decrease indicating that NOS3 expression could become self-attenuated by co-expressed intronic 27 nt-ncRNA. Reporter assay results and phylogenetic analyses enabled us to propose a novel model for STAT3-3'-UTR targeting by this 27-nt-ncRNA. CONCLUSIONS: An adverse intrauterine environment leads to adaptive changes of NOS3 expression. Apparently, a rapid NOS3 self-limiting response upon ectopic triggers co-exists with longer termed expression changes in response to placental insufficiency involving differential epigenetic signatures. Their persistence might contribute to impaired vascular endothelial response and consequently increase the risk of cardiovascular disease later in life.
