Choice of Frontline Tyrosine-Kinase Inhibitor and Early Events in Very Elderly Patients With Chronic Myeloid Leukemia in Chronic Phase: A "Campus CML" Study.

OBJECTIVES: The study aimed to evaluate the utilization of frontline TKI therapy in a large cohort of elderly CP-CML patients. METHODS: A retrospective analysis was conducted on 332 CP-CML patients aged 75 years or older among 1929 diagnosed from January 2012 to December 2019 followed at 36 participating Hematology Centers involved in the "Campus CML" project. RESULTS: Among the patients analyzed, 85.8% received imatinib (IM) while 14.2% received second-generation TKIs (2G-TKI), 59.5% dasatinib, and 40.5% nilotinib. Most patients initiated IM at standard dose (67.3%) while 32.7% at reduced dose. A similar trend was observed with 2G-TKIs. The cumulative incidence of permanent TKI discontinuation at 12 months was 28.4%, primarily due to primary resistance (10.1%) and extra-hematologic toxicity (9.5%), with no significant difference between IM and 2G-TKI groups. Following the introduction of generic IM in Italy in 2018, IM usage increased significantly compared with 2G-TKIs. CONCLUSIONS: IM was in our Centers the preferred frontline therapy for older CP-CML patients, with increasing utilization after the introduction of generic formulations. However, 2G-TKIs are still used in a substantial proportion of patients, suggesting individualized physician assessments regarding patient suitability and expectations. Further investigation is needed to assess efficacy and safety of reduced TKI doses in this patient population.

Measles associated with international travel in the region of the Americas, Australia and Europe, 2001-2013: a systematic review.

BACKGROUND: Travel volumes are still increasing resulting in a more interconnected world and fostering the spread of infectious diseases. We aimed to evaluate the relevance of travel-related measles, a highly transmissible and vaccine-preventable disease. METHOD: Between 2001 and 2013, surveillance and travel-related measles data were systematically reviewed according to the PRISMA guidelines with extraction of relevant articles from Medline, Embase, GoogleScholar and from public health authorities in the Region of the Americas, Europe and Australia. RESULTS: From a total of 960 records 44 articles were included and they comprised 2128 imported measles cases between 2001 and 2011. The proportion of imported cases in Europe was low at 1-2%, which reflects the situation in a measles-endemic region. In contrast, imported and import-related measles accounted for up to 100% of all cases in regions with interrupted endemic measles transmission. Eleven air-travel related reports described 132 measles index cases leading to 47 secondary cases. Secondary transmission was significantly more likely to occur if the index case was younger or when there were multiple infectious cases on board. Further spread to health care settings was found. Measles cases associated with cruise ship travel or mass gatherings were sporadically observed. CONCLUSIONS: Within both, endemic and non-endemic home countries, pretravel health advice should assess MMR immunity routinely to avoid measles spread by nonimmune travelers. To identify measles spread as well as to increase and sustain high vaccination coverages joint efforts of public health specialists, health care practitioners and travel medicine providers are needed.

The integration of the risk management process with the lifecycle of medical device software.

OBJECTIVES: The application of software in the Medical Device (MD) domain has become central to the improvement of diagnoses and treatments. The new European regulations that specifically address software as an important component of MD, require complex procedures to make software compliant with safety requirements, introducing thereby new challenges in the qualification and classification of MD software as well as in the performance of risk management activities. Under this perspective, the aim of this paper is to propose an integrated framework that combines the activities to be carried out by the manufacturer to develop safe software within the development lifecycle based on the regulatory requirements reported in US and European regulations as well as in the relevant standards and guidelines. METHODS: A comparative analysis was carried out to identify the main issues related to the application of the current new regulations. In addition, standards and guidelines recently released to harmonise procedures for the validation of MD software have been used to define the risk management activities to be carried out by the manufacturer during the software development process. RESULTS: This paper highlights the main issues related to the qualification and classification of MD software, providing an analysis of the different regulations applied in Europe and the US. A model that integrates the risk management process within the software development lifecycle has been proposed too. It is based on regulatory requirements and considers software risk analysis as a central input to be managed by the manufacturer already at the initial stages of the software design, in order to prevent MD failures. CONCLUSIONS: Relevant changes in the process of MD development have been introduced with the recognition of software being an important component of MDs as stated in regulations and standards. This implies the performance of highly iterative processes that have to integrate the risk management in the framework of software development. It also makes it necessary to involve both medical and software engineering competences to safeguard patient and user safety.

Is workflow technology suitable to represent and manage clinical trials?

The clinical trial has to be rigidly followed because it identifies a uniform clinical behaviour, which has to be adopted by the different physicians carrying out the test. The life cycle of the clinical trial is therefore based on a planning and definition phase, a next experimental phase connected with its diffusion to the involved centres and finally an evaluation phase of the results. An information system, which supports the users in the different phases of the clinical trial life cycle, has to take into account the different characteristics of each phase. The aim of this paper is to illustrate the role of WF technology as a component of an information system which supports the life cycle of a clinical trial also on the basis of the experience of the Italian Group for Haematological Disease of Adults (GIMEMA).

A system for the description of healthcare guidelines.

Contained costs and quality of treatment are two elements which have to be considered when planning and controlling both clinical and managerial activities of healthcare structures (HCSs). Each structure has to be marked by a high level of quality of treatment and by specific professional competencies and skills of its operators. It is therefore fundamental to provide a system which supports the management of processes and of guidelines which characterise an healthcare structure. In this paper we present a system able to describe processes of an HCS and in particular clinical guidelines. This system is based on a workflow conceptual model, able to represent clinical and managerial activities carried out in HCSs (the Atreus model).

A conceptual representation of clinical and managerial guidelines: the ATREUS workflow model.

In this paper we propose a workflow conceptual model able to represent clinical and managerial activities within healthcare structures, the ATREUS model. This model uses: a) a graphical representation which models the activities and the events that activate them; b) a textual representation of information related to: a set of conditions used for the control of activity execution; the actors who undertake the activity; the resources and tools necessary for its enactment, the clinical and managerial data generated by the activity execution; c) a state diagram which allows the control of the activity execution. The model allows modularity, activity nesting and temporal flexibility using a top-down refinement of processes. This model, unlike others, makes it possible to highlight the different types of decision involved in the performance of an activity.

Extending the standard architecture for healthcare units: the guideline server.

The main topic of our research is health care unit (HCU) reengineering. To this aim, a guideline oriented conceptual model of HCUs was developed. In order to map this conceptual model into an information system with a client-server architecture, a guideline server is needed. The guideline concept and its life cycle are introduced and the main functions of the guideline server are presented.

Modeling the management of protocols as the kernel of a healthcare information system.

A conceptual model of a health care structure is described. The management of protocols viewed as structured, flexible, and coherent descriptions of activities aimed to solve specific problems in the system is the kernel of the model. A global approach to the protocols is proposed. Each protocol is modeled from two points of view: the nature of the actions (clinical, administrative, programming, and control) and the life cycle of protocols (theoretical, customized, and performed). In our approach the patient folder not only records information about the patient, but also contains and controls the execution of the protocols planned to be performed on the patient. As a consequence, all aspects related to protocol execution are chronologically reported in the folder in a federated manner. In this way the patient folder becomes a complex, multifaceted object, able to capture all information needed to evaluate the patient evolution in a given period.