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.

Parental evaluation of a telemonitoring service for children with Type 1 Diabetes.

Introduction In the past years, we developed a telemonitoring service for young patients affected by Type 1 Diabetes. The service provides data to the clinical staff and offers an important tool to the parents, that are able to oversee in real time their children. The aim of this work was to analyze the parents' perceived usefulness of the service. Methods The service was tested by the parents of 31 children enrolled in a seven-day clinical trial during a summer camp. To study the parents' perception we proposed and analyzed two questionnaires. A baseline questionnaire focused on the daily management and implications of their children's diabetes, while a post-study one measured the perceived benefits of telemonitoring. Questionnaires also included free text comment spaces. Results Analysis of the baseline questionnaires underlined the parents' suffering and fatigue: 51% of total responses showed a negative tendency and the mean value of the perceived quality of life was 64.13 in a 0-100 scale. In the post-study questionnaires about half of the parents believed in a possible improvement adopting telemonitoring. Moreover, the foreseen improvement in quality of life was significant, increasing from 64.13 to 78.39 ( p-value = 0.0001). The analysis of free text comments highlighted an improvement in mood, and parents' commitment was also proved by their willingness to pay for the service (median = 200 euro/year). Discussion A high number of parents appreciated the telemonitoring service and were confident that it could improve communication with physicians as well as the family's own peace of mind.

Standardization of immunotherapy adverse events in patient information leaflets and development of an interface terminology for outpatients' monitoring.

INTRODUCTION: Immunotherapy is effective for treating cancer, but it is also associated with a wide spectrum of adverse events. In order to detect them early, the patients need to be monitored at home, between the therapy administrations, e.g., by asking them to report outcomes, usually including symptoms and quality of life measures. For the collected data to be reusable, the symptoms need to be in a standardized form. The aim of this study is to explore the standardization of the information contained in the patient information leaflets (PILs) of immunotherapy drugs, by creating an interface terminology of immunotherapy-related adverse events, which should support a consistent collection of symptoms from the patients. METHODS: PILs contain a significant amount of information in free text, but they mix patient-reportable and clinically assessable events. We extracted a list of patient-reportable adverse events, mapped them to reference terminologies and compared the mapping results to choose the best-performing reference terminology. RESULTS: The PILs standardization led to the extraction of 151 symptoms and 424 terms, including both preferred terms and synonyms in English and Italian. Among the reference terminologies we considered, SNOMED CT allowed us to map all concepts and became, hence, the main reference terminology for the resulting interface terminology. A preliminary validation on the PIL of a new immunotherapy drug showed that our interface terminology already contained all the mentioned symptoms. CONCLUSION: PILs provide a valuable source for determining adverse events. The resulting interface terminology includes Italian and English terms for patient-reportable adverse events for five immunotherapy drugs representative of their category. Further work will be undertaken to evaluate the usability of the interface terminology and the patients' experience and satisfaction with the proposed terms, made available for example through an app, as well as its effectiveness on data quality and quality of care.

Personalization and Patient Involvement in Decision Support Systems: Current Trends.

OBJECTIVES: This survey aims at highlighting the latest trends (2012-2014) on the development, use, and evaluation of Information and Communication Technologies (ICT) based decision support systems (DSSs) in medicine, with a particular focus on patient-centered and personalized care. METHODS: We considered papers published on scientific journals, by querying PubMed and Web of ScienceTM. Included studies focused on the implementation or evaluation of ICT-based tools used in clinical practice. A separate search was performed on computerized physician order entry systems (CPOEs), since they are increasingly embedding patient-tailored decision support. RESULTS: We found 73 papers on DSSs (53 on specific ICT tools) and 72 papers on CPOEs. Although decision support through the delivery of recommendations is frequent (28/53 papers), our review highlighted also DSSs only based on efficient information presentation (25/53). Patient participation in making decisions is still limited (9/53), and mostly focused on risk communication. The most represented medical area is cancer (12%). Policy makers are beginning to be included among stakeholders (6/73), but integration with hospital information systems is still low. Concerning knowledge representation/management issues, we identified a trend towards building inference engines on top of standard data models. Most of the tools (57%) underwent a formal assessment study, even if half of them aimed at evaluating usability and not effectiveness. CONCLUSIONS: Overall, we have noticed interesting evolutions of medical DSSs to improve communication with the patient, consider the economic and organizational impact, and use standard models for knowledge representation. However, systems focusing on patient-centered care still do not seem to be available at large.

Multicenter outpatient dinner/overnight reduction of hypoglycemia and increased time of glucose in target with a wearable artificial pancreas using modular model predictive control in adults with type 1 diabetes.

AIMS: To test in an outpatient setting the safety and efficacy of continuous subcutaneous insulin infusion (CSII) driven by a modular model predictive control (MMPC) algorithm informed by continuous glucose monitoring (CGM) measurement. METHODS: 13 patients affected by type 1 diabetes participated to a non-randomized outpatient 42-h experiment that included two evening meals and overnight periods (in short, dinner & night periods). CSII was patient-driven during dinner & night period 1 and MMPC-driven during dinner&night period 2. The study was conducted in hotels, where patients could move around freely. A CGM system (G4 Platinum; Dexcom Inc., San Diego, CA, USA) and insulin pump (AccuChek Combo; Roche Diagnostics, Mannheim, Germany) were connected wirelessly to a smartphone-based platform (DiAs, Diabetes Assistant; University of Virginia, Charlottesville, VA, USA) during both periods. RESULTS: A significantly lower percentage of time spent with glucose levels <3.9 mmol/l was achieved in period 2 compared with period 1: 1.96 ± 4.56% vs 12.76 ± 15.84% (mean ± standard deviation, p < 0.01), together with a greater percentage of time spent in the 3.9-10 mmol/l target range: 83.56 ± 14.02% vs 62.43 ± 29.03% (p = 0.04). In addition, restricting the analysis to the overnight phases, a lower percentage of time spent with glucose levels <3.9 mmol/l (1.92 ± 4.89% vs 12.7 ± 19.75%; p = 0.03) was combined with a greater percentage of time spent in 3.9-10 mmol/l target range in period 2 compared with period 1 (92.16 ± 8.03% vs 63.97 ± 2.73%; p = 0.01). Average glucose levels were similar during both periods. CONCLUSIONS: The results suggest that MMPC managed by a wearable system is safe and effective during evening meal and overnight. Its sustained use during this period is currently being tested in an ongoing randomized 2-month study.

Gquest: modeling patient questionnaires and administering them through a mobile platform application.

BACKGROUND: The use of surveys is becoming popular in the health care industry for acquiring information useful to the accomplishment of several studies. Besides their exploitation on a large scale for conducting epidemiological studies, surveys are being increasingly carried out on a narrower perspective through the administration of questionnaires aimed at assessing the quality of life perceived by patients or their clinical status during mid- or long-term treatments. This is useful for managing resources or optimizing and individualizing treatments. OBJECTIVES: This paper describes Gquest, a platform for modeling, generating and administering questionnaires through mobile devices such as smartphones or tablets. Gquest was motivated by the need of administering questionnaires during home treatments, albeit its applicability is rather general. The main requirement was to have a very simple, clean and easy to use platform able to support (a) physicians in the design and delivery of questionnaires and (b) outpatients in sending self-recorded outcomes to the clinical staff. METHODS: Gquest has two basic components. The first one is a model devised for representing questionnaires which is extremely flexible. It allows the generation of questions and answers of different types, supports adaptivity in the dialog with the user and enforces simple consistency rules for checking his input. The second component is an application able to run instances of those questionnaires. It downloads questionnaires over the air in terms of XML files from a server and stores them locally into the mobile repository. Questionnaires become then available to the user, who in our case is a patient or one of his relatives. The user can select which one to fill-in, according to his needs and/or the specific treatment protocol. The selected questionnaire may be filled-in all at once or be completed in subsequent steps over time since any input provided is persisted on a local database. Finally, when a questionnaire is closed all the answers are transparently synchronized to a server for further evaluation or statistical purposes. RESULTS: The platform has been exploited and tested in two medical domains where questionnaires have very different purposes; a quality of life pilot survey involving patients with atrial fibrillation within the EU-funded project MobiGuide, and an investigation of the users' needs during the requirements elicitation phase of a telemedicine project for the safe discharge of fragile patients. CONCLUSIONS: Gquest proved to be a suitable tool for dealing with a wide variety of question types and has been positively accepted by the patients enrolled in the pilot study.

Flexible guideline-based patient careflow systems.

Workflow Management Systems integrate domain and organisational knowledge to support business processes. When applied to the medical environment, they can be termed "Careflow Management Systems", and may be used to manage care delivery by enhancing co-operation among healthcare professionals. This paper focuses on care delivery based on clinical practice guidelines. Healthcare organisations are very different from industrial or commercial companies: their main goal is not profit, but maintaining and improving the health of the public. Therefore, outcomes are difficult to measure. Firstly, physicians, while playing a variety of roles, are quite independent decision-makers; secondly, the object of the process, i.e. the patient, may be involved in choosing treatment options, and may be treated by different institutions. For these reasons, the standard functionality of typical Workflow Management Systems must be strongly enhanced in order to cope with healthcare delivery needs. A major issue is accounting for exceptions. In most non-clinical settings this is not a problem because processes are very well defined and can often be easily controlled by some higher authority. As explained above, this does not happen in healthcare organisations. Responsibilities are widely shared, and health care professionals may be non-compliant with guidelines for a variety of reasons. The paper presents a classification of possible exceptions, and shows how the sequence of tasks described by a guideline may be altered, at the implementation level, in order to meet actual user needs, while maintaining guideline intentions as much as possible. A terminology server is also exploited towards this end. This work illustrates a prototype of a Careflow Management System based on an international guideline for ischemic stroke treatment, developed by the American Heart Association.

A framework for building cooperative software agents in medical applications.

Exploiting the information technology may have a great impact on improving cooperation and interoperability among the different professionals taking part to the process of delivering health care services. New paradigms are therefore being devised considering software systems as autonomous agents able to help professionals in accomplishing their duties. To this aim those systems should encapsulate the skills for solving a given set of tasks and possess the social ability to cooperate in order to fetch the required information and knowledge. This paper illustrates a methodology facilitating the development of interoperable intelligent software agents for medical applications and proposes a generic computational model for implementing them. That model may be specialized in order to support all the different information and knowledge related requirements of a Hospital Information System. The architecture is being tested for implementing a prototype system able to coordinate the joint efforts of the professionals involved in managing patients affected by Acute Myeloid Leukemia.

Towards cooperative patient management through organizational and medical ontologies.

Within knowledge and data engineering a new research paradigm is emerging based on the Multi-Agent System (MAS) architectural framework, allowing human and software agents to interoperate and thus cooperate within common application areas. In such a framework, knowledgeable agents of heterogeneous nature, that possess diverse but at least partially compatible or inter-translatable conceptual views, or ontologies, modeling both their own expertise and the external environment, make somehow available their information resources or problem-solving abilities for cooperative processes addressing the construction of a new agent or the achievement of some common goal through a correlated execution of tasks. In this paper, we restrict our analysis to the case of an organization of cognitive agents, illustrated with examples from a prototypical healthcare MAS, that is, a so-called Distributed Healthcare Information System (D-HIS). The prototype makes use of an ontological library written in the standard language Ontolingua. An ongoing application of the methodology to the main problem of Clinical Practice Guidelines (GLs) computer-based dissemination and enforcement is described.

A development environment for knowledge-based medical applications on the World-Wide Web.

The World-Wide Web (WWW) is increasingly being used as a platform to develop distributed applications, particularly in contexts, such as medical ones, where high usability and availability are required. In this paper we propose a methodology for the development of knowledge-based medical applications on the web, based on the use of an explicit domain ontology to automatically generate parts of the system. We describe a development environment, centred on the LISPWEB Common Lisp HTTP server, that supports this methodology, and we show how it facilitates the creation of complex web-based applications, by overcoming the limitations that normally affect the adequacy of the web for this purpose. Finally, we present an outline of a system for the management of diabetic patients built using the LISPWEB environment.

Building patient workflow management systems by integrating medical and organizational knowledge.

Patient management is a distributed activity involving general practitioners, clinicians, analysts, nurses, etc. Thus an integrated Patient Workflow Management System (WfMS), based on a detailed model of both the organizational and medical knowledge, could heavily improve Health Care System's performance in terms of collaborative work and resource utilization. A set of tools was developed to improve 1) acquisition of medical knowledge represented through clinical practice Guideline, and 2) acquisition of organizational knowledge describing the work process.

An ontology-based multi-agent architecture for distributed health-care information systems.

Managing patients in a shared-care context is a knowledge-intensive activity. To support cooperative work in medical care, computer technology should both augment the capabilities of individual specialists and enhance their ability of interacting with each other and with computational resources. Thus, a major shift is needed from centralized first generation health-care information systems to distributed environments composed of several interconnected agents, cooperating in maintaining a full track of the patient clinical history and supporting health-care providers in all the phases of the patient-management process. This paper outlines a general methodology to make architectural choices while designing or integrating new software components into a distributed health-care information system. A particular stress is laid on the specification of shared conceptual models, or ontologies, providing agents committing to them with the common semantic foundation required for effective interoperation.

Ontology and terminology servers in agent-based health-care information systems.

A new research paradigm is emerging based on the multi-agent system architectural framework, allowing human and software agents to interoperate and thus cooperate within common application areas. Within a multi-agent system, the different "views of the world" of knowledgeable agents are to be bridged through their commitment to common ontologies and terminologies. We developed a general methodology for the design or integration of new components into a Health-care Information System conceived as a network of software and human agents. In our view, ontological and terminological services are entrusted to dedicated agents, namely ontology and terminology servers, allowing the configuration of suitable application ontologies for distributed applications. The role is described that such servers, operatively coordinated in order to preserve semantic coherence, should play within a distributed Health-care Information System.

Knowledge-acquisition tools for medical knowledge-based systems.

Knowledge-based systems (KBS) have been proposed to solve a large variety of medical problems. A strategic issue for KBS development and maintenance are the efforts required for both knowledge engineers and domain experts. The proposed solution is building efficient knowledge acquisition (KA) tools. This paper presents a set of KA tools we are developing within a European Project called GAMES II. They have been designed after the formulation of an epistemological model of medical reasoning. The main goal is that of developing a computational framework which allows knowledge engineers and domain experts to interact cooperatively in developing a medical KBS. To this aim, a set of reusable software components is highly recommended. Their design was facilitated by the development of a methodology for KBS construction. It views this process as comprising two activities: the tailoring of the epistemological model to the specific medical task to be executed and the subsequent translation of this model into a computational architecture so that the connections between computational structures and their knowledge level counterparts are maintained. The KA tools we developed are illustrated taking examples from the behavior of a KBS we are building for the management of children with acute myeloid leukemia.

Inferential knowledge acquisition.

This paper describes the approach we are pursuing for modeling inferential processes in knowledge-based systems. It is aimed at overcoming the lack of generality affecting many of the systems described in the literature. This mainly happens since the problem-solving method adopted by those systems is too closely tied to the particular domain problem over which the method itself has been modeled. We also describe a system called M-KAT (Medical Knowledge Acquisition Tool) which is useful in simplifying the process of acquiring inferential knowledge. M-KAT relies on an epistemological model of medical reasoning which represents a generalization of most of the problem-solving methods adopted in medical knowledge-based systems. The metarules formalism has been adopted as a mean for representing inferential knowledge and making its acquisition easier, thus allowing the computational implementation of the epistemological model of medical reasoning.

A specialized framework for medical diagnostic knowledge-based systems.

For a knowledge-based system (KBS) to exhibit an intelligent behavior, it must be endowed with knowledge enabling it to represent the expert's strategies. The elicitation task is inherently difficult for strategic knowledge, because strategy is often tacit, and, even when it has been made explicit, it is not an easy task to describe it in a form which may be directly translated and implemented into a program. This paper describes a Specialized Framework for Medical Diagnostic Knowledge-Based Systems that can help an expert in the process of building KBSs in a medical domain. The framework is based on an epistemological model of diagnostic reasoning which has proven to be helpful in describing the diagnostic process in terms of the tasks that it is composed of. It allows a straightforward modeling of diagnostic reasoning at the knowledge level by the domain expert, thus helping to convey domain-dependent strategies into the target KBS.

A specialized framework for Medical Diagnostic Knowledge Based Systems.

To have a knowledge based system (KBS) exhibiting an intelligent behavior, it must be endowed even with knowledge able to represent the expert's strategies, other than with domain knowledge. The elicitation task is inherently difficult for strategic knowledge, because strategy is often tacit, and, even when it has been made explicit, it is not an easy task to describe it in a form that may be directly translated and implemented into a program. This paper describes a Specialized Framework for Medical Diagnostic Knowledge Based Systems able to help an expert in the process of building KBSs in a medical domain. The framework is based on an epistemological model of diagnostic reasoning which has proved to be helpful in describing the diagnostic process in terms of the tasks by which it is composed of.

NEOANEMIA: a knowledge-based system emulating diagnostic reasoning.

Medical diagnosis can be modeled in terms of the classical notions of abduction, deduction, and induction. Abduction is making a preliminary guess that allows one to establish a set of plausible diagnostic hypotheses, followed by deduction for exploring their consequences and induction for testing the hypotheses with available patient data or for planning the acquisition of new data. Such a description of diagnostic reasoning at a knowledge level helps the construction of an expert system by fashioning the adopted expert system building tool to reflect the structure of the problem rather than by fitting the problem to the tool. To this aim, reasoning strategies need to be represented abstractly, separate from medical facts and relations, to make the design more transparent and explainable.