Additional booster doses in patients with chronic lymphocytic leukemia induce humoral and cellular immune responses to SARS-CoV-2 similar to natural infection regardless ongoing treatments: A study by ERIC, the European Research Initiative on CLL.

Profound immune dysregulation and impaired response to the SARS-CoV-2 vaccine put patients with chronic lymphocytic leukemia (CLL) at risk of severe COVID-19. We compared humoral memory and T-cell responses after booster dose vaccination or breakthrough infection. (Green) Quantitative determination of anti-Spike specific antibodies. Booster doses increased seroconversion rate and antibody titers in all patient categories, ultimately generating humoral responses similar to those observed in the postinfection cohort. In detail, humoral response with overscale median antibody titers arose in >80% of patients in watch and wait, off-therapy in remission, or under treatment with venetoclax single-agent. Anti-CD20 antibodies and active treatment with BTK inhibitors (BTKi) represent limiting factors of humoral response, still memory mounted in ~40% of cases following booster doses or infection. (Blue) Evaluation of SARS-CoV-2-specific T-cell responses. Number of T-cell functional activation markers documented in each patient. The vast majority of patients, including those seronegative, developed T-cell responses, qualitatively similar between treatment groups or between vaccination alone and infection cases. These data highlight the efficacy of booster doses in eliciting T-cell immunity independently of treatment status and support the use of additional vaccination boosters to stimulate humoral immunity in patients on active CLL-directed treatments.

Abstraction on clinical data sequences: an object-oriented data model and a query language based on the event calculus.

In this work, we deal with temporal abstraction of clinical data. Abstractions are, for example, blood pressure state (e.g. normal, high, low) and trend (e.g. increasing, decreasing and stationary) over time intervals. The goal of our work is to provide clinicians with automatic tools to extract high-level, concise, important features of available collections of time-stamped clinical data. This capability is especially important when the available collections constantly increase in size, as in long-term clinical follow-up, leading to information overload. The approach we propose exploits the integration of the deductive and object-oriented approaches in clinical databases. The main result of this work is an object-oriented data model based on the event calculus to support temporal abstraction. The proposed approach has been validated building the CARDIOTABS system for the abstraction of clinical data collected during echocardiographic tests.

Managing different time granularities of clinical information by an interval-based temporal data model.

In the field of databases, time management at different levels of granularity has been an issue for several years, for instance when dealing with clinical information from different databases using different time units, dealing with natural language expressions, or when dealing with temporal uncertainty. A temporal data model is proposed to manage the temporal aspect of data, presented at various and mixed levels of granularity. The concept of temporal assertions shapes the entire temporal information. The model provides a temporal dimension to the data by using intervals that can be specified at different granularities. The model supports a three-valued logic, where True, False and Undefined are the truth values. The temporal data model allows to manage some degrees of uncertainty when establishing temporal relationships between intervals or between temporal assertions, expressed at different granularities. The logical connectives and quantifiers can manage each of the three truth-values. We applied the temporal data model by implementing an object-oriented database system for managing follow-up clinical data from patients who underwent percutaneous transluminal coronary angioplasty.

MS2/Cardio: towards a multi-service medical software for cardiology.

Many clinics are interested to use software packages in daily practice, but lack of integration of such packages seriously limits their scope. In practice this often entails switching between programs and interrupting the run of an individual program. A multi-task approach would not solve this problem as it would not eliminate the need to input the same data many times, as often occurs when using separate packages. The construction of a Multi-Service Medical Software package (MSx2) is described, which was also developed as an example of practical integration of some clinically relevant functions. The package runs on a personal computer in an MS-DOS environment and integrates a time-oriented medical record management unit (TOMRU) for data of ambulatory patients, and a drug information management unit (DIMU) concerning posology, content, effects, and possible interactions. Of the possible database configurations allowed by MSx2, the cardiology patient database (MSx2/C) and hypertensive patient database (MSx2/H) were developed and described here. Clinical information to be included in the configurations was obtained after discussion and consensus of clinical practitioners. MSx2/C was distributed to several hundred clinical centers during computerized courses to train future users. MSx2 can easily transfer patient data to statistical processing packages.

TANCLICO: tools for the analysis of inter-departmental clinical communications.

Patient care management provided by healthcare organizations is complex, involving many different care providers. The information exchange between providers concerns a varying and considerable number of actors and a high transmission load. Based on models, used to characterize specific features of work processes, we propose a new method able to analyze and represent clinical communications inside hospitals. Software has been developed, providing tools for storing and retrieving information resulting from clinical communications. The method, together with data collected in actual situations, may constitute useful tools for health information systems developers.

Applying object-oriented technologies in modeling and querying temporally oriented clinical databases dealing with temporal granularity and indeterminacy.

The need of managing temporal information given at different levels of granularity or with indeterminacy is common to many application areas. Among them, we focus on clinical data management. Different time granularities and indeterminacy are also needed in querying temporal databases. In this paper, we describe GCH-OSQL (Granular Clinical History-Object Structured Query Language), an object-oriented temporally-oriented extension of SQL. GCH-OSQL is based on an object-oriented temporal data model, GCH-OODM. GCH-OODM allows storage of clinical information at different and mixed granularities or with temporal indeterminacy. GCH-OSQL deals with the valid time of clinical information. The temporal extension of the SELECT construct includes the addition of the TIME-SLICE and MOVING WINDOW clauses, and the capability to reference the temporal dimension of objects in the WHERE and SELECT clauses. Using object-oriented technologies, a system prototype for GCH-OSQL and GCH-OODM has been implemented and applied to data management of follow-up patients after coronary angioplasty intervention.

Data compression applied to dynamic electrocardiography.

We have tested some techniques of ECG compression on the BIH/MIT Arrhythmias database. We have applied the following methods: (1) method of differences; (2) compression by prediction; (3) sample skipping methods; with the following kinds of errors: amplitude error, amplitude and delay error, area error. In the first and second method the average code length found after application of the Huffmann encoding has been found to be about 4 bits sample-1. For the third method the final compression ratio varies according to the allowed error; with a limited error threshold, however, we have reached an average compression a little lower than 1:5.

Angiocardiographic digital still images compressed via irreversible methods: concepts and experiments.

We defined, implemented and tested two new methods for irreversible compression of angiocardiographic still images: brightness error limitation (BEL) and pseudo-gradient adaptive brightness and contrast error limitation (PABCEL). The scan path used to compress the digital images is based on the Peano-Hilbert plane-filling curve. The compression methods limit, for each pixel, the brightness errors introduced when approximating the original image (i.e. the difference between the values of corresponding pixels as grey levels). Additional limitations are imposed to the contrast error observed when considering along the scan path consecutive pixels of both the original and the reconstructed image. After previous testing on angiocardiographic images selected as clinically significant from 35 mm films, we enlarged our experiment to a set of 38 coronary angiograms digitally acquired. BEL and PABCEL methods were experimented according to several values of the implied thresholds. Up to a compression ratio of 9:1 for the BEL method and 10:1 for the PABCEL method, no deterioration of the reconstructed images were detected by human observers. After a visual evaluation, we performed a quantitative evaluation. The visualization of pseudo-colour difference images showed the capability of BEL and PABCEL for preserving the most significant clinical details of the original images. For comparison, we applied the JPEG (joint photographic experts group) image-compression standard to the same set of images. In this case, pseudo-colour difference images showed a homogeneous distribution of errors on the image surface. Quantitative compression results obtained by testing the different methods are comparable, but, unlike JPEG, BEL and PABCEL methods allow the user to keep under his direct control the maximum error allowed at each single pixel of the original image. These different behaviors are confirmed by the values obtained for the considered numerical quality quantifiers.

TEODOLINDA. A communication architecture for hospital information systems.

This paper is focused on a system for the release and distribution of messages and services among hospital units, which extends hospital information systems features in the field of communication and supports hospital organisation to fulfil healthcare commitments.

Some experiments in compressing angiocardiographic images according to the Peano-Hilbert scan path.

We defined and implemented three new irreversible compression techniques for digital angiocardiographic static images: brightness error limitation (BEL), pseudo-gradient adaptive brightness error limitation (PABEL), pseudo-gradient adaptive brightness and contrast error limitation (PABCEL). To scan digital images we implemented an algorithm based on the Peano-Hilbert plane filling curve. We applied our compression techniques to 168 static images selected from angiocardiographic 35-mm films. We achieved best compression results applying the PABCEL method, obtaining a mean compression ratio of about 8:1. Consulted cardiologists did not find significant diagnostic differences between original images and reconstructed ones.

Temporal reasoning and temporal data maintenance in medicine: issues and challenges.

We present a brief, nonexhaustive overview of research efforts in designing and developing time-oriented systems in medicine. The growing volume of research on time-oriented systems in medicine can be viewed from either an application point of view, focusing on different generic tasks (e.g. diagnosis) and clinical areas (e.g. cardiology), or from a methodological point of view, distinguishing between different theoretical approaches. In this overview, we focus on highlighting methodological and theoretical choices, and conclude with suggestions for new research directions. Two main research directions can be noted: temporal reasoning, which supports various temporal inference tasks (e.g. temporal abstraction, time-oriented decision support, forecasting, data validation), and temporal data maintenance, which deals with storage and retrieval of data that have heterogeneous temporal dimensions. Efforts common to both research areas include the modeling of time, of temporal entities, and of temporal queries. We suggest that tasks such as abstraction of time-oriented data and the handling of different temporal-granularity levels should provide common ground for collaboration between the two research directions and fruitful areas for future research.

A database schema for public-domain medical software.

The quantity of public-domain medical software available is huge, and a classification schema may be therefore helpful. We developed a schema that includes identification data (name of the software, author, etc.), description (hardware and software requirements), classification (software category, application domain, etc.) and evaluation data (external quality and internal quality factors). The schema was tested on the public-domain software available at the SCAMC meetings (about 36 Mb). We also classified the software by employing students from a master course in computer science and medical informatics. We stored the high quantity of information collected in a database we developed using Paradox.

WWW-based access to object-oriented clinical databases: the KHOSPAD project.

KHOSPAD is a project aiming at improving the quality of the process of patient care concerning general practitioner-patient-hospital relationships, using current information and networking technologies. The studied application field is a cardiology division, with hemodynamic laboratory and the population of PTCA patients. Data related to PTCA patients are managed by ARCADIA, an object-oriented database management system developed for the considered clinical setting. We defined a remotely accessible view of ARCADIA medical record, suitable for general practitioners (GPs) caring patients after PTCA, during the follow-up period. Using a PC, a modem and Internet, an authorized GP can consult remotely the medical records of his PTCA patients. Main features of the application are related to the management and display of complex data, specifically characterized by multimedia and temporal features, based on an object-oriented temporal data model.

Timing is everything. Time-oriented clinical information systems.

Time is important in clinical information systems. Representing, maintaining, querying, and reasoning about time-oriented clinical data is a major theoretical and practical research area in medical informatics. In this nonexhaustive overview, we present a brief synopsis of research efforts in designing and developing time-oriented information systems in medicine. These efforts can be viewed from either an application point of view, distinguishing between different clinical tasks (such as diagnosis versus therapy) and clinical areas (such as infectious diseases versus oncology), or a methodological point of view, distinguishing between different theoretical approaches. We also explore the two primary methodological and theoretical paths research has taken in the past decade: temporal reasoning and temporal data maintenance. Both of these research areas include efforts to model time, temporal entities, and temporal queries. Collaboration between the two areas is possible, through tasks such as the abstraction of raw time-oriented clinical data into higher-level meaningful clinical concepts and the management of different levels of temporal granularity. Such collaboration could provide a common ground and useful areas for future research and development. We conclude with our view of future research directions.

ARCADIA: a system for the integration of angiocardiographic data and images by an object-oriented DBMS.

Use of data base techniques to store medical records has been going on for more than 40 years. Some aspects still remain unresolved, e.g., the management of textual data and image data within a single system. Object-orientation techniques applied to a database management system (DBMS) allow the definition of suitable data structures (e.g., to store digital images): some facilities allow the use of predefined structures when defining new ones. Currently available object-oriented DBMS, however, still need improvements both in the schema update and in the query facilities. This paper describes a prototype of a medical record that includes some multimedia features, managing both textual and image data. The prototype here described considers data from the medical records of patients subjected to percutaneous transluminal coronary artery angioplasty. We developed it on a Sun workstation with a Unix operating system and ONTOS as an object-oriented DBMS.

Supporting temporal queries on clinical relational databases: the S-WATCH-QL language.

Due to the ubiquitous and special nature of time, specially in clinical datábases there's the need of particular temporal data and operators. In this paper we describe S-WATCH-QL (Structured Watch Query Language), a temporal extension of SQL, the widespread query language based on the relational model. S-WATCH-QL extends the well-known SQL by the addition of: a) temporal data types that allow the storage of information with different levels of granularity; b) historical relations that can store together both instantaneous valid times and intervals; c) some temporal clauses, functions and predicates allowing to define complex temporal queries.

Object-orientated DBMS techniques for time-oriented medical record.

In implementing time-orientated medical record (TOMR) management systems, use of a relational model played a big role. Many applications have been developed to extend query and data manipulation languages to temporal aspects of information. Our experience in developing TOMR revealed some deficiencies inside the relational model, such as: (a) abstract data type definition; (b) unified view of data, at a programming level; (c) management of temporal data; (d) management of signals and images. We identified some first topics to face by an object-orientated approach to database design. This paper describes the first steps in designing and implementing a TOMR by an object-orientated DBMS.

Dissemination, standardization and user-flexibility in implementing TOMRs for cardiology.

A great many clinics are interested in using software programs in daily practice. We report on the construction of a time oriented medical record unit (TOMRU). It runs on MS-DOS personal computers. TOMRU handles the follow-up data of ambulatory patients. Of the possible database customizations allowed by TOMRU, the cardiology patient database (TOMRU/C) and hypertensive patient database (TOMRU/H) were developed and are described here. Customizing TOMRU should in any case be left to an expert user, in charge of database management. The clinical information to be included in the customizations was obtained by discussing the needs of and obtaining the consensus of clinical practitioners. TOMRU/C was handed over to some hundreds of clinical centres during the computerized itinerant courses held to train users.

Querying temporal clinical databases with different time granularities: the GCH-OSQL language.

There is a need for managing temporal clinical information given at different levels of granularity. Different time granularities are also needed in querying clinical databases. In this paper, we describe GCH-OSQL (Granular Clinical History--Object Structured Query Language), an object-oriented temporally-oriented extension of SQL. GCH-OSQL is based on an object-oriented temporal data model. It allows storage of clinical information at different and mixed granularities. GCH-OSQL deals with the valid time of clinical information. GCH-OSQL offers also a graphical user-interface. It guides different end users, from expert to naive, to formulate expressive and correct queries.

Managing and displaying different time granularities of clinical information.

We approach the need of representing by powerful graphical user-interface the granularity of the temporal clinical information. In this work we present some contributions, to suitably display such temporal clinical information. The graphical representation relies on a temporal clinical data model able to manage data having different granularities.