Temporal detection and analysis of guideline interactions

Background Clinical practice guidelines (CPGs) are assuming a major role in the medical area, to grant the quality of medical assistance, supporting physicians with evidence-based information of interventions in the treatment of single pathologies. The treatment of patients affected by multiple diseases (comorbid patients) is one of the main challenges for the modern healthcare. It requires the development of new methodologies, supporting physicians in the treatment of interactions between CPGs. Several approaches have started to face such a challenging problem. However, they suffer from a substantial limitation: they do not take into account the temporal dimension. Indeed, practically speaking, interactions occur in time. For instance, the effects of two actions taken from different guidelines may potentially conflict, but practical conflicts happen only if the times of execution of such actions are such that their effects overlap in time. Objectives We aim at devising a methodology to detect and analyse interactions between CPGs that considers the temporal dimension. Methods In this paper, we first extend our previous ontological model to deal with the fact that actions, goals, effects and interactions occur in time, and to model both qualitative and quantitative temporal constraints between them. Then, we identify different application scenarios, and, for each of them, we propose different types of facilities for user physicians, useful to support the temporal detection of interactions. Results We provide a modular approach in which different Artificial Intelligence temporal reasoning techniques, based on temporal constraint propagation, are widely exploited to provide users with such facilities. We applied our methodology to two cases of comorbidities, using simplified versions of CPGs. Conclusion We propose an innovative approach to the detection and analysis of interactions between CPGs considering different sources of temporal information (CPGs, ontological knowledge and execution logs), which is the first one in the literature that takes into account the temporal issues, and accounts for different application scenarios

Reasoning and querying bounds on differences with layered preferences

Artificial intelligence largely relies on bounds on differences (BoDs) to model binary constraints regarding different dimensions, such as time, space, costs, and calories. Recently, some approaches have extended the BoDs framework in a fuzzy, \u201cnoncrisp\u201d direction, considering probabilities or preferences. While previous approaches have mainly aimed at providing an optimal solution to the set of constraints, we propose an innovative class of approaches in which constraint propagation algorithms aim at identifying the \u201cspace of solutions\u201d (i.e., the minimal network) with their preferences, and query answering mechanisms are provided to explore the space of solutions as required, for example, in decision support tasks. Aiming at generality, we propose a class of approaches parametrized over user\u2010defined scales of qualitative preferences (e.g., Low, Medium, High, and Very High), utilizing the resume and extension operations to combine preferences, and considering different formalisms to associate preferences with BoDs. We consider both \u201cgeneral\u201d preferences and a form of layered preferences that we call \u201cpyramid\u201d preferences. The properties of the class of approaches are also analyzed. In particular, we show that, when the resume and extension operations are defined such that they constitute a closed semiring, a more efficient constraint propagation algorithm can be used. Finally, we provide a preliminary implementation of the constraint propagation algorithms

GLARE-SSCPM: an Intelligent System to Support the Treatment of Comorbid Patients

The development of software tools supporting physicians in the treatment of comorbid patients is a challenging goal and a hot topic in Medical Informatics and Artificial Intelligence. Computer Interpretable Guidelines (CIGs) are consolidated tools to support physicians with evidence-based recommendations in the treatment of patients affected by a specific disease. However, the applications of two or more CIGs on comorbid patients is critical, since dangerous interactions between (the effects of) actions from different CIGs may arise. GLARE-SSCPM is the first tool supporting, in an integrated way, (i) the knowledge-based detection of interactions, (ii) the management of the interactions, and (iii) the final merge of (part of) the CIGs operating on the patient. GLARE-SSCPM is characterized by being very supportive to physicians, providing them support for focusing, interaction detection, and for an hypothesize and test approach to manage the detected interactions. To achieve such goals, it provides advanced Artificial Intelligence techniques. Preliminary tests in the educational context, within the RoPHS project, have provided encouraging results

Aerodynamics of a short intake in crosswind

The next generation of turbofan aero-engines are likely to have an increase in fan diameter to reduce the specific thrust and increase the overall propulsive efficiency. More compact nacelles with possibly shorter intakes may be used to reduce weight and drag and achieve a net reduction of fuel consumption. For these compact nacelles a key consideration is the design of the short intake at the off-design conditions such as crosswind and high incidence operations. The close coupled interaction between a short intake and the fan at these off-design conditions is one of the key challenges. Previous work focused on the impact of short intake aerodynamics on the fan but there is a similar requirement to understand the impact of the fan on the viable short intake design space. This paper addresses the influence of the fan on the separation onset of the flow within a short intake under crosswind conditions. The effect of the fan on the separation characteristics of the intake boundary layer was considered both from a steady and an unsteady point of view. A hierarchy of fan computational models was used to separately assess the different aerodynamic contributions and to evaluate a net effect of the fan on the intake critical condition. Steady computational fluid dynamics analyses showed a notable positive effect of the fan on total pressure loss at post-separation conditions relative to a configuration without the fan. However, unsteady analyses revealed that fan unsteadiness has an adverse impact on the intake separation characteristics which reduces the intake critical conditions by about 15%. The main mechanisms behind the unsteady interaction were identified. Overall this work addresses, for the first time, the role of fan unsteadiness on the separation characteristics of the boundary layer within a short intake in crosswind

One-carbon pathway metabolites are altered in the plasma of subjects with Down syndrome: Relation to chromosomal dosage

Introduction: Down syndrome (DS) is the most common chromosomal disorder and it is caused by trisomy of chromosome 21 (Hsa21). Subjects with DS show a large heterogeneity of phenotypes and the most constant clinical features present are typical facies and intellectual disability (ID). Several studies demonstrated that trisomy 21 causes an alteration in the metabolic profile, involving among all the one-carbon cycle. Methods: We performed enzyme-linked immunosorbent assays (ELISAs) to identify the concentration of 5 different intermediates of the one-carbon cycle in plasma samples obtained from a total of 164 subjects with DS compared to 54 euploid subjects. We investigated: tetrahydrofolate (THF; DS n = 108, control n = 41), 5-methyltetrahydrofolate (5-methyl-THF; DS n = 140, control n = 34), 5-formyltetrahydrofolate (5-formyl-THF; DS n = 80, control n = 21), S-adenosyl-homocysteine (SAH; DS n = 94, control n = 20) and S-adenosyl-methionine (SAM; DS n = 24, control n = 15). Results: Results highlight specific alterations of THF with a median concentration ratio DS/control of 2:3, a decrease of a necessary molecule perfectly consistent with a chromosomal dosage effect. Moreover, SAM and SAH show a ratio DS/control of 1.82:1 and 3.6:1, respectively. Discussion: The relevance of these results for the biology of intelligence and its impairment in trisomy 21 is discussed, leading to the final proposal of 5-methyl-THF as the best candidate for a clinical trial aimed at restoring the dysregulation of one-carbon cycle in trisomy 21, possibly improving cognitive skills of subjects with DS

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Economic consequences of investing in anti-HCV antiviral treatment from the Italian NHS perspective : a real-world-based analysis of PITER data

OBJECTIVE: We estimated the cost consequence of Italian National Health System (NHS) investment in direct-acting antiviral (DAA) therapy according to hepatitis C virus (HCV) treatment access policies in Italy. METHODS: A multistate, 20-year time horizon Markov model of HCV liver disease progression was developed. Fibrosis stage, age and genotype distributions were derived from the Italian Platform for the Study of Viral Hepatitis Therapies (PITER) cohort. The treatment efficacy, disease progression probabilities and direct costs in each health state were obtained from the literature. The break-even point in time (BPT) was defined as the period of time required for the cumulative costs saved to recover the Italian NHS investment in DAA treatment. Three different PITER enrolment periods, which covered the full DAA access evolution in Italy, were considered. RESULTS: The disease stages of 2657 patients who consecutively underwent DAA therapy from January 2015 to December 2017 at 30 PITER clinical centres were standardized for 1000 patients. The investment in DAAs was considered to equal €25 million, €15 million, and €9 million in 2015, 2016, and 2017, respectively. For patients treated in 2015, the BPT was not achieved, because of the disease severity of the treated patients and high DAA prices. For 2016 and 2017, the estimated BPTs were 6.6 and 6.2 years, respectively. The total cost savings after 20 years were €50.13 and €55.50 million for 1000 patients treated in 2016 and 2017, respectively. CONCLUSIONS: This study may be a useful tool for public decision makers to understand how HCV clinical and epidemiological profiles influence the economic burden of HCV