Trusting telemedicine: A discussion on risks, safety, legal implications and liability of involved stakeholders.

OBJECTIVES: The main purpose of the article is to raise awareness among all the involved stakeholders about the risks and legal implications connected to the development and use of modern telemedicine systems. Particular focus is given to the class of "active" telemedicine systems, that imply a real-world, non-mediated, interaction with the final user. A secondary objective is to give an overview of the European legal framework that applies to these systems, in the effort to avoid defensive medicine practices and fears, which might be a barrier to their broader adoption. METHODS: We leverage on the experience gained during two international telemedicine projects, namely MobiGuide (pilot studies conducted in Spain and Italy) and AP@home (clinical trials enrolled patients in Italy, France, the Netherlands, United Kingdom, Austria and Germany), whose development our group has significantly contributed to in the last 4 years, to create a map of the potential criticalities of active telemedicine systems and comment upon the legal framework that applies to them. Two workshops have been organized in December 2015 and March 2016 where the topic has been discussed in round tables with system developers, researchers, physicians, nurses, legal experts, healthcare economists and administrators. RESULTS: We identified 8 features that generate relevant risks from our example use cases. These features generalize to a broad set of telemedicine applications, and suggest insights on possible risk mitigation strategies. We also discuss the relevant European legal framework that regulate this class of systems, providing pointers to specific norms and highlighting possible liability profiles for involved stakeholders. CONCLUSIONS: Patients are more and more willing to adopt telemedicine systems to improve home care and day-by-day self-management. An essential step towards a broader adoption of these systems consists in increasing their compliance with existing regulations and better defining responsibilities for all the involved stakeholders.

Increased fetal blood pressure response to maternal norepinephrine after pharmacological inhibition of norepinephrine uptake in pregnant sheep.

OBJECTIVE: Norepinephrine (NE) is elevated in pregnancies complicated by preeclampsia (PE). Specific uptake of NE by the NE transporter (NET) plays a central role as regulator of NE levels. Expression of NET is reduced in placentas from PE pregnancies. To study adverse fetal effects of reduced NET expression on the placental buffering capacity, the NET was pharmacologically blocked by a specific uptake inhibitor reboxetine. STUDY DESIGN: We evaluated the effect of NE uptake inhibition on maternal and fetal arterial blood pressure responses to increasing maternal doses of NE in 10 chronically prepared fetal sheep. Arterial blood pressure was monitored continuously during increasing doses of i.v. NE. RESULTS: NET inhibition increased both fetal and maternal mean arterial blood pressure (p < 0.001, respectively). CONCLUSION: Reuptake by NET appears to be a mechanism protecting the fetus from NE. A reduced uptake capacity in preeclamptic pregnancies due to reduced NE uptake may lead to increased fetal arterial blood pressure.

Norepinephrine transporter (NET), serotonin transporter (SERT), vesicular monoamine transporter (VMAT2) and organic cation transporters (OCT1, 2 and EMT) in human placenta from pre-eclamptic and normotensive pregnancies.

Pre-eclampsia is one of the most common causes of perinatal and maternal morbidity and mortality. High blood pressure and proteinuria are important clinical signs of pre-eclampsia. Sympathetic overactivity and elevated level of circulating vaso active substances, such as monoamines has been shown. Extracellular concentrations of monoamines are normally kept low by specific transporter proteins of which many are expressed in the placenta. In this study we used in situ hybridization and real-time PCR to study the gene expression of monoamine transporters, such as NET, SERT, VMAT2, EMT and OCT1/2, in normal as well as in pre-eclamptic placentae. We demonstrated high expression of NET mRNA in the trophoblast cells of the anchoring villi and a lower expression intensity in the chorionic villi. SERT mRNA was mainly detected in chorionic villi. VMAT2 mRNA was not detected in the central part of the placenta but was present in the spiral arteries of placenta bed biopsies, in cytokeratin positive cells. EMT mRNA was mainly detected in the intra lobular septa and together with OCT1 and OCT2 mRNAs also expressed in scattered cells of placental vessel adventitias. Moreover, quantitative analysis showed a significant lower expression of NET and EMT mRNAs in pre-eclamptic placentae as compared to the control group. A defective gene expression or function of these monoamines transporters might explain the elevated concentrations of monoamines in pre-eclamptic patients. Monoamine transporters may serve as a protective mechanism preventing vasoconstriction in the placental vascular bed and thereby securing a stable blood flow to the fetus.