A framework for automated conflict detection and resolution in medical guidelines

This research is supported by the MRC-funded UK Research and Innovation grant MR/S003819/1 and by EPSRC grant EP/M014290/1.Common chronic conditions are routinely treated following standardised procedures known as clinical guidelines. For patients suffering from two or more chronic conditions, known as multimorbidity, several guidelines have to be applied simultaneously, which may lead to severe adverse effects when the combined recommendations and prescribed medications are inconsistent or incomplete. This paper presents an automated formal framework to detect, highlight and resolve conflicts in the treatments used for patients with multimorbidities focusing on medications. The presented extended framework has a front-end which takes guidelines captured in a standard modelling language and returns the visualisation of the detected conflicts as well as suggested alternative treatments. Internally, the guidelines are transformed into formal models capturing the possible unfoldings of the guidelines. The back-end takes the formal models associated with multiple guidelines and checks their correctness with a theorem prover, and inherent inconsistencies with a constraint solver. Key to our approach is the use of an optimising constraint solver which enables us to search for the best solution that resolves/minimises conflicts according to medication efficacy and the degree of severity in case of harmful combinations, also taking into account their temporal overlapping. The approach is illustrated throughout with a real medical example.Publisher PDFPeer reviewe

Patients and doctors group meetings: an innovative way to explore severe asthma backstage

Severe asthma patients' life is heavily influenced by the disease, which has impact on personal and professional choic-es or general lifestyle. Despite the available tools to help physicians investigating the patient-reported outcomes there is a need for a more standardised and structured approach to include the evaluation of quality of life together with the emotions of patients into the routine clinical interaction. We hereby report the use of an active listening and insight approach to understand the emotions of patients with severe asthma through dedicated in-person meetings involving a group of patients with their doctors, caregivers and an external moderator. The initiative "Patients insight meeting" was organized within 17 specialist referral centres for severe asthma in Italy in 2019 and involved 149 patients. Insights related to 4 different items were collected and a task force composed by the external moderators produced a general report including the suggestions from the participating centres. This experience of group-meetings involving both patients and doctors together represents an innovative way to investigate real life experience and the emotions of asthmatic patients, highlighting unmet needs related to patient's experience of his/her disease that need to be included in severe asthmatics' management strategy

Biological treatments in allergy: Prescribing patterns and management of hypersensitivity reactions

Clinical Communication

Dupilumab Efficacy on Asthma Functional, Inflammatory, and Patient-Reported Outcomes across Different Disease Phenotypes and Severity: A Real-Life Perspective

Dupilumab is currently approved for the treatment of Type 2 severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). Few studies have specifically reported on dupilumab efficacy on asthma outcomes as a primary objective in a real-life setting, in patients with and without CRSwNP. Our study aimed to explore the efficacy of dupilumab on functional, inflammatory, and patient-reported outcomes in asthma patients across different disease phenotypes and severity, including mild-to-moderate asthma coexisting with CRSwNP. Data from 3, 6, and 12 months follow-up were analyzed. Asthma (FEV1%, Tiffeneau%, ACT, FeNO, oral steroid use, exacerbation rate, and blood eosinophilia) and polyposis (SNOT22, VAS, NPS) outcomes showed a rapid (3 months) and sustained (6 and 12 months) significant change from baseline, despite most of the patients achieving oral steroid withdrawal. According to the sensitivity analysis, the improvement was not conditioned by either the presence of polyposis or severity of asthma at baseline. Of note, even in the case of milder asthma forms, a significant further improvement was recorded during dupilumab treatment course. Our report provides short-, medium-, and long-term follow-up data on asthma outcomes across different diseases phenotypes and severity, contributing to the real-world evidence related to dupilumab efficacy on upper and lower airways T2 inflammation

About Bianchi I with VSL

In this paper we study how to attack, through different techniques, a perfect fluid Bianchi I model with variable G,c and Lambda, but taking into account the effects of a $c$-variable into the curvature tensor. We study the model under the assumption,div(T)=0. These tactics are: Lie groups method (LM), imposing a particular symmetry, self-similarity (SS), matter collineations (MC) and kinematical self-similarity (KSS). We compare both tactics since they are quite similar (symmetry principles). We arrive to the conclusion that the LM is too restrictive and brings us to get only the flat FRW solution. The SS, MC and KSS approaches bring us to obtain all the quantities depending on \int c(t)dt. Therefore, in order to study their behavior we impose some physical restrictions like for example the condition q<0 (accelerating universe). In this way we find that $c$ is a growing time function and Lambda is a decreasing time function whose sing depends on the equation of state, w, while the exponents of the scale factor must satisfy the conditions $\sum_{i=1}^{3}\alpha_{i}=1$ and $\sum_{i=1}^{3}\alpha_{i}^{2}<1,$ $\forall\omega$, i.e. for all equation of state$,$ relaxing in this way the Kasner conditions. The behavior of $G$ depends on two parameters, the equation of state $\omega$ and $\epsilon,$ a parameter that controls the behavior of $c(t),$ therefore $G$ may be growing or decreasing.We also show that through the Lie method, there is no difference between to study the field equations under the assumption of a $c-$var affecting to the curvature tensor which the other one where it is not considered such effects.Nevertheless, it is essential to consider such effects in the cases studied under the SS, MC, and KSS hypotheses.Comment: 29 pages, Revtex4, Accepted for publication in Astrophysics & Space Scienc

Unlocking the Long-Term Effectiveness of Benralizumab in Severe Eosinophilic Asthma: A Three-Year Real-Life Study

Background: Benralizumab has been shown to restore good control of severe eosinophilic asthma (SEA). Robust data on benralizumab effectiveness over periods longer than 2 years are scarce. Methods: This retrospective multicentric study was conducted on 108 Italian SEA patients treated with benralizumab for up to 36 months. Partial and complete clinical remission (CR) were assessed. Data were analyzed with descriptive statistics or using linear, logistic, and negative binomial mixed-effect regression models. Results: At 36 months, benralizumab reduced the exacerbation rate by 89% and increased the forced expiratory volume in 1 second (FEV1) (+440 mL at 36 months, p &lt; 0.0001). Benralizumab improved asthma control as well as sinonasal symptoms in patients with chronic rhinosinusitis with nasal polyposis (CRSwNP). Up to 93.33% of patients either reduced or discontinued OCS; benralizumab also decreased ICS use and other asthma medications. Overall, 84.31% of patients achieved partial or complete CR. Conclusions: Benralizumab improved asthma and sinonasal outcomes up to 36 months. These findings support the potential of benralizumab to induce CR, emphasizing its role as a disease-modifying anti-asthmatic drug for the management of SEA. Further research is warranted to expand these findings by minimizing data loss and assessing benralizumab’s long-term safety

The Effects of Social Ties on Coordination: Conceptual Foundations for an Empirical Analysis

International audienceThis paper investigates the influence that social ties can have on behavior. After defining the concept of social ties that we consider, we introduce an original model of social ties. The impact of such ties on social preferences is studied in a coordination game with outside option. We provide a detailed game theoretical analysis of this game while considering various types of players, i.e., self-interest maximizing, inequity averse, and fair agents. In addition to these approaches that require strategic reasoning in order to reach some equilibrium, we also present an alternative hypothesis that relies on the concept of team reasoning. After having discussed the differences between the latter and our model of social ties, we show how an experiment can be designed so as to discriminate among the models presented in the paper

The role of chest CT in deciphering interstitial lung involvement: systemic sclerosis versus COVID-19

Objective: The aim of this study was to identify the main CT features that may help in distinguishing a progression of interstitial lung disease (ILD) secondary to SSc from COVID-19 pneumonia. // Methods: This multicentric study included 22 international readers grouped into a radiologist group (RADs) and a non-radiologist group (nRADs). A total of 99 patients, 52 with COVID-19 and 47 with SSc-ILD, were included in the study. // Results: Fibrosis inside focal ground-glass opacities (GGOs) in the upper lobes; fibrosis in the lower lobe GGOs; reticulations in lower lobes (especially if bilateral and symmetrical or associated with signs of fibrosis) were the CT features most frequently associated with SSc-ILD. The CT features most frequently associated with COVID- 19 pneumonia were: consolidation (CONS) in the lower lobes, CONS with peripheral (both central/peripheral or patchy distributions), anterior and posterior CONS and rounded-shaped GGOs in the lower lobes. After multivariate analysis, the presence of CONs in the lower lobes (P < 0.0001) and signs of fibrosis in GGOs in the lower lobes (P < 0.0001) remained independently associated with COVID-19 pneumonia and SSc-ILD, respectively. A predictive score was created that was positively associated with COVID-19 diagnosis (96.1% sensitivity and 83.3% specificity). // Conclusion: CT diagnosis differentiating between COVID-19 pneumonia and SSc-ILD is possible through a combination of the proposed score and radiologic expertise. The presence of consolidation in the lower lobes may suggest COVID-19 pneumonia, while the presence of fibrosis inside GGOs may indicate SSc-ILD

SANI definition of Clinical Remission in Severe Asthma: a Delphi consensus

: Severe Asthma affects about 10% of the asthmatic population, and it is characterized by a low lung function and a higher count of blood leucocytes, mainly eosinophils. To date, various definitions are used in clinical practice and in the literature to identify asthma remission: clinical remission, inflammatory remission, and complete remission. The aim of this work is to highlight a consensus for asthma remission using a Delphi method. In the context of SANI (Severe Asthma Network Italy), accounting for 57 Severe Asthma Centers and more then 2200 patients, a Board of six expert drafted a list of candidate statements in a questionnaire, which has been revised to minimize redundancies and ensure clear and consistent wording for the first round (R1) of the analysis. 32 statements have been included in the R1 questionnaire, and then submitted to a panel of 80 experts, which used a 5-points Likert scale to measure their agreement to each statement. Then, an Interim Analysis of R1 data have been performed, items were discussed and considered to produce a consistent questionnaire for the round 2 (R2) of the analysis. After this, the Board set the R2 questionnaire, which included only the important key topics. Panelists have been asked to vote the statements in the R2 questionnaire afterwards. During R2, the criteria of complete clinical remission (the absence of need for OCS, symptoms, exacerbations/attacks, and a pulmonary function stability) and those of partial clinical remission (the absence of need for OCS, and 2 out of 3 criteria: the absence of symptoms, exacerbations/attacks, and a pulmonary stability) were confirmed. This SANI Delphi Analysis defined a valuable, independent and easy to use tool to test the efficacy of different treatments in patients with severe asthma enrolled into the SANI registry

The role of chest CT in deciphering interstitial lung involvement: systemic sclerosis versus COVID-19

Objective: The aim of this study was to identify the main CT features that may help in distinguishing a progression of interstitial lung disease (ILD) secondary to SSc from COVID-19 pneumonia. Methods: This multicentric study included 22 international readers grouped into a radiologist group (RADs) and a non-radiologist group (nRADs). A total of 99 patients, 52 with COVID-19 and 47 with SSc-ILD, were included in the study. Results: Fibrosis inside focal ground-glass opacities (GGOs) in the upper lobes; fibrosis in the lower lobe GGOs; reticulations in lower lobes (especially if bilateral and symmetrical or associated with signs of fibrosis) were the CT features most frequently associated with SSc-ILD. The CT features most frequently associated with COVID- 19 pneumonia were: consolidation (CONS) in the lower lobes, CONS with peripheral (both central/peripheral or patchy distributions), anterior and posterior CONS and rounded-shaped GGOs in the lower lobes. After multivariate analysis, the presence of CONs in the lower lobes (P < 0.0001) and signs of fibrosis in GGOs in the lower lobes (P < 0.0001) remained independently associated with COVID-19 pneumonia and SSc-ILD, respectively. A predictive score was created that was positively associated with COVID-19 diagnosis (96.1% sensitivity and 83.3% specificity). Conclusion: CT diagnosis differentiating between COVID-19 pneumonia and SSc-ILD is possible through a combination of the proposed score and radiologic expertise. The presence of consolidation in the lower lobes may suggest COVID-19 pneumonia, while the presence of fibrosis inside GGOs may indicate SSc-ILD