An Architecture for Providing Personalized Digital Health.

Patients need mechanisms to integrate health information coming from different sources, including personal devices. This would lead to Personalized Digital Health (PDH). HIPAMS (Health Information Protection And Management System) is a modular and interoperable secure architecture that helps in achieving this objective and building a Framework for PDH. The paper presents HIPAMS and how it supports PDH.

MedSecurance Project: Advanced Security-for-Safety Assurance for Medical Device IoT (IoMT).

The MedSecurance project focus on identifying new challenges in cyber security with focus on hardware and software medical devices in the context of emerging healthcare architectures. In addition, the project will review best practice and identify gaps in the guidance, particularly the guidance stipulated by the medical device regulation and directives. Finally, the project will develop comprehensive methodology and tooling for the engineering of trustworthy networks of inter-operating medical devices, that shall have security-for-safety by design, with a strategy for device certification and certifiable dynamic network composition, ensuring that patient safety is safeguarded from malicious cyber actors and technology "accidents".

FAIR Aspects of a Health Information Protection and Management System.

BACKGROUND: Privacy management is a key issue when dealing with storage and distribution of health information. However, FAIR (Findability, Accessibility, Interoperability, and Reusability) principles when sharing information are in increasing demand in several organizations, especially for information generated in public-funded research projects. OBJECTIVES: The two main objectives of the presented work are the definition of a secure and interoperable modular architecture to manage different kinds of medical content (xIPAMS [x, for Any kind of content, Information Protection And Management System] and HIPAMS [Health Information Protection And Management System]), and the application of FAIR principles to that architecture in such a way that privacy and security are compatible with FAIR. METHODS: We propose the concept of xIPAMS as a modular architecture, following standards for interoperability, which defines mechanisms for privacy, protection, storage, search, and access to health-related information. RESULTS: xIPAMS provides FAIR principles and preserves patient's privacy. For each module, we identify how FAIR principles apply. CONCLUSIONS: We have analyzed how xIPAMS, and in particular HIPAMS (Health content), support the FAIR principles focusing on security and privacy. We have identified the FAIR principles supported by the different xIPAMS modules, concluding that the four principles are supported. Our analysis has also considered a possible implementation based on the concept of DACS (Document Access and Communication System), a system storing medical documents in a private and secure way. In addition, we have analyzed security aspects of the FAIRification process and how they are provided by xIPAMS modules.

Provenance and Dynamic Consents for the Management of Medical Data.

Medical data describe patient health information, both in healthy and disease conditions. In any case, health institutions need to ask for patient consent in order to provide their services. Patients usually give consent on a one-time basis, for a specific usage. Afterwards, if medical data usage is research, original patient consent does not apply and further consents should be required. On the other hand, provenance of medical data to verify the origin of health procedures is desirable, as digital health is increasing. We propose HIPAMS modular architecture to provide both provenance and dynamic consents for medical data as described in this paper.

Implementation of Privacy and Security for a Genomic Information System Based on Standards.

Genomic information is a very sensitive type of digital information as it not only applies to a person, but also to close relatives. Therefore, privacy provision is key to protecting genomic information from unauthorized access. It is worth noting that most of the current genomic information formats do not provide specific mechanisms by which to secure the stored information. In order to solve, among other things, the privacy provision issue, we proposed the GIPAMS (Genomic Information Protection And Management System) modular architecture, which is based on the use of standards such as ISO/IEC 23092 and a few GA4GH (Global Alliance for Genomics and Health) initiatives. Some of the GIPAMS modules have already been implemented, mainly based on ISO/IEC 23092 features, and we are conducting work on the complete version of the architecture, and other standards are also considered. One of the objectives of GIPAMS is to enable the management of different formats of genomic information in a unique and interoperable way, providing privacy and security for formats that do not currently support them.

Implementation of Privacy and Security for a Genomic Information System.

Genomic information is key for the implementation of real personalized medicine. Nevertheless, access to this kind of information must be controlled because of its high privacy and security requirements. Several genomic information formats exist, although we have started from MPEG-G as it includes metadata and protection mechanisms since its inception and provides a hierarchical structure to organize the information contained. The proposed GIPAMS modular architecture provides a secure and controlled access to genomic information, which may help on improving personalized medicine as described in this paper.

FAIR Aspects of a Genomic Information Protection and Management System.

To handle genomic information while supporting FAIR principles, we present GIPAMS, a modular architecture. GIPAMS provides security and privacy to manage genomic information by means of several independent services and modules that interact among them in an orchestrated way. The paper analyzes how some security and privacy aspects of the FAIRification process are covered by the GIPAMS platform.

Retrieval and treatment of patients with primary biliary cholangitis who are lost in the health system.

INTRODUCTION: hepatitis C patients loss to follow-up in the health care system has been shown to have negative consequences. This study aimed to investigate this issue as regards primary biliary cholangitis. METHODS: the databases (immunology, biochemistry, clinical reports, drug dispensation, appointments) of 4 reference hospitals in Spain (serving a population of 1,450,000 inhabitants) were analyzed. The diagnosis of primary biliary cholangitis was based on an antimitochondrial antibody titer ≥ 1:80, chronically elevated alkaline phosphatase, and the absence of other liver disease. Patients were classified as lost in the absence of reports indicating a diagnosis, specific medical follow-up, and/or treatment with bile salts. RESULTS: a total of 1372 patients with antimitochondrial antibody titers ≥ 1:80 were included between January 2010 and June 2019. A total of 697 (50.8 %) were classified as having primary biliary cholangitis, and 100 patients (14.3 %; 95 % CI: 11.8-17.2) were identified as lost. Of these, 30 were contacted and retrieved. The median age was 70 years, 93 % were female, median alkaline phosphatase was 185 IU/L, 10 % had pruritus, and 27 % had a transient elastography value > 9.5 kPa. The disease was confirmed and ursodeoxycholic acid was started in all 30 patients. Death was liver-related in 6 of the 100 patients classified as lost. CONCLUSION: up to 14.3 % of patients (1 out of 7) with a definitive diagnosis of primary biliary cholangitis remain undiagnosed, thus preventing monitoring and treatment. More than a quarter are at risk of advanced liver disease and its complications. Patients lost in the system must be identified and retrieved, and searching hospital databases is a suitable approach to meet this goal.

Security and Privacy when Applying FAIR Principles to Genomic Information.

Making data Findable, Accessible, Interoperable and Reusable (FAIR) is a good approach when data needs to be shared. However, security and privacy are still critical aspects. In the FAIRification process, there is a need both for de-identification of data and for license attribution. The paper analyses some of the issues related to this process when the objective is sharing genomic information. The main results are the identification of the already existing standards that could be used for this purpose and how to combine them. Nevertheless, the area is quickly evolving and more specific standards could be specified.

Adding Security and Privacy to Genomic Information Representation.

Provision of security and privacy to genomic data is a key issue in current genomic information representation. Existing formats do not give a solution to these issues (or they provide a partial one), so new solutions are demanded. MPEG-G (ISO/IEC 23092, Genomic Information Representation) is an International Standard for the representation of genomic information being defined by the MPEG Committee (Moving Pictures Expert Group, ISO/IEC JTC1 SC29/WG11). We provide flexible protection to the information stored inside the MPEG-G format with a combination of security techniques and privacy rules.

Metadata to Describe Genomic Information.

Interoperable metadata is key for the management of genomic information. We propose a flexible approach that we contribute to the standardization by ISO/IEC of a new format for efficient and secure compressed storage and transmission of genomic information.

Protecting Privacy of Genomic Information.

The ISO/IEC committee in charge of standardizing the well-known MPEG audiovisual standards has launched, in cooperation with the ISO committee on Biotechnology, a new activity for efficient compressed storage and transmission of genomic information. The paper presents proposals for adding privacy and security to such in-progress standards.

Security and Privacy in a DACS.

The management of electronic health records (EHR), in general, and clinical documents, in particular, is becoming a key issue in the daily work of Healthcare Organizations (HO). The need for providing secure and private access to, and storage for, clinical documents together with the need for HO to interoperate, raises a number of issues difficult to solve. Many systems are in place to manage EHR and documents. Some of these Healthcare Information Systems (HIS) follow standards in their document structure and communications protocols, but many do not. In fact, they are mostly proprietary and do not interoperate. Our proposal to solve the current situation is the use of a DACS (Document Archiving and Communication System) for providing security, privacy and standardized access to clinical documents.

Privacy provision in eHealth using external services.

Privacy provision is a key issue for successful secure access to patients' health information. Current approaches do not always provide patients with the ability to define suitable rules to access to their information in a secure way. This paper presents an approach to give patients control over their information by means of external services. In this way, health information management and access control are kept independent and more secure.

Identification of serologically silent occult hepatitis C virus infection by detecting immunoglobulin G antibody to a dominant HCV core peptide epitope.

BACKGROUND/AIMS: Occult HCV infection has been described among anti-HCV-HCV RNA-negative individuals with abnormal transaminase values in whom HCV RNA is detected in liver. METHODS: IgG antibody to an HCVcore-derived peptide (anti-HCVcore) was investigated in 145 patients with serologically silent occult HCV infection. RESULTS: At the time of the diagnostic biopsy 45/145 (31%) occult HCV-infected patients tested IgG anti-HCVcore-positive but none of the 140 patients with HCV-unrelated liver disease (P<0.001). Among 23 IgG anti-HCVcore-positive patients at baseline, 22 remained antibody-reactive (one became antibody-negative). Similarly, 17/31 baseline anti-HCVcore-negative patients remained non-reactive whereas 14 seroconverted to IgG anti-HCVcore (although transiently in 10 patients). Thus, a total of 59/145 (40.7%) patients with occult HCV infection showed IgG anti-HCVcore reactivity at any time point analyzed, including 14 initially non-reactive patients. By supplemental immunoblot assay 16 sera reacted weakly with an HCVcore-peptide band (indeterminate result) of which 10 (62.5%) reacted in the IgG anti-HCVcore assay. Occult HCV-infected patients who tested anti-HCVcore-positive showed more frequently signs of necro-inflammation (P=0.035) and greater percentages of HCV RNA-positive hepatocytes (P=0.004) compared with those anti-HCVcore-negative. CONCLUSIONS: This work documents that IgG anti-HCVcore testing identifies occult HCV infection among seronegative, non-viremic patients using screening tests and may be useful in tracking anti-HCV-negative infections.

Cellular immune responses associated with occult hepatitis C virus infection of the liver.

Occult hepatitis C virus (HCV) infection is a type of recently identified chronic infection that is evidenced only by detection of HCV RNA in liver; patients consistently test negative for antibodies to HCV and HCV RNA in serum. Using ex vivo and in vitro measures of T-cell responses, we have identified functional virus-specific memory CD4(+) and CD8(+) T cells in the peripheral blood of patients with occult HCV infection. The features of the virus-specific T cells were consistent with immune surveillance functions, supporting previous exposure to HCV. In addition, the magnitudes of CD4(+) and CD8(+) T-cell responses were in parallel and correlated inversely with the extent of liver HCV infection. The detection of HCV-specific T cells in individuals in whom HCV RNA can persist in the liver despite the absence of viremia and antibodies indicates that HCV replication is prolonged in the face of virus-specific CD4(+) and CD8(+) T-cell responses. These findings demonstrate that HCV-specific cellular immune responses are markers not only of previous exposure to and recovery from HCV but also of ongoing occult HCV infection.

Virus-specific T-cell responses associated with hepatitis C virus (HCV) persistence in the liver after apparent recovery from HCV infection.

Hepatitis C virus (HCV) RNA persistence in the liver has been described even after apparent resolution of HCV infection. Because T-cell reactivity plays a role in recovery from HCV infection, virus-specific T-cell responses were investigated in apparently recovered individuals in whom hepatic HCV RNA persistence was documented: 15 sustained virological responders to interferon (IFN)-treatment and 9 asymptomatic aviremic anti-HCV carriers. HCV-specific CD4(+) T-cell proliferative responses were detected significantly more often in apparently recovered individuals (sustained virological responders: 60%; asymptomatic anti-HCV carriers: 66%) compared with 50 chronic hepatitis C patients (28%; P < 0.05). However, T-cell frequencies and numbers tended to decline over time and the number of HCV proteins targeted by CD4(+) T-cell proliferative responses was limited. Interestingly, liver viral load correlated inversely with virus-specific immune responses. Thus, CD4(+) T-cell responders showed significantly lower hepatic HCV RNA levels (P < 0.05). HCV-specific IFN-gamma-secreting CD4(+) T-cells were not detected in all the apparently recovered patients although they were found significantly more often compared with chronic hepatitis C patients (P < 0.05). Also, HCV NS3-specific CD8(+) T-cells were detected in 11 HLA-A2-positive apparently recovered individuals (8 sustained virological responders and 3 asymptomatic anti-HCV carriers); T-cell frequencies tended to be greater in those patients who had lower hepatic viral levels. In conclusion, HCV-specific T-cells are detectable in apparently recovered individuals in whom HCV RNA can persist in the liver indicating that HCV replication may be prolonged in the face of an insufficient or inadequate virus-specific CD4(+) and CD8(+) T-cell response.