Harrodian Instability and Learning

It is a standard result in macroeconomic models populated by boundedly-rational agents that the stability of equilibria is left undetermined by the deep structural parameters, because it depends upon the nature of the prevailing beliefs. Apparently, a mean of avoiding this sort of indeterminacy is making belief formation endogenous, via methods and results borrowed from the learning literature. The paper attempts at clarifying the difficulties encountered by this line of argument when predictions of a variable are based on expectation functions defined on a space of realized values of the same variable and learning is based on gradient descent procedures. Since the analysis is carried out with reference to a simple macroeconomic model of Harrodian inspiration, the paper gives also some local results on the theme of Harrodian instabiliity

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

Severe refractory asthma: Current treatment options and ongoing research

Patients with severe asthma have a greater risk of asthma-related symptoms, morbidities, and exacerbations. Moreover, healthcare costs of patients with severe refractory asthma are at least 80% higher than those with stable asthma, mainly because of a higher use of healthcare resources and chronic side effects of oral corticosteroids (OCS). The advent of new promising biologicals provides a unique therapeutic option that could achieve asthma control without OCS. However, the increasing number of available molecules poses a new challenge: the identification and selection of the most appropriate treatment. Thanks to a better understanding of the basic mechanisms of the disease and the use of predictive biomarkers, especially regarding the Th2-high endotype, it is now easier than before to tailor therapy and guide clinicians toward the most suitable therapeutic choice, thus reducing the number of uncontrolled patients and therapeutic failures. In this review, we will discuss the different biological options available for the treatment of severe refractory asthma, their mechanism of action, and the overlapping aspects of their usage in clinical practice. The availability of new molecules, specific for different molecular targets, is a key topic, especially when considering that the same targets are sometimes part of the same phenotype. The aim of this review is to help clarify these doubts, which may facilitate the clinical decision-making process and the achievement of the best possible outcomes

Walking distance on 6-MWT is a prognostic factor in idiopathic pulmonary fibrosis

Background and aim of the work: Idiopathic pulmonary fibrosis (IPF) is a progressive disease with high mortality rates and a median survival of 2-3 years from time of diagnosis. The prognosis for any individual patient, however, is variable. To elucidate the clinical significance of 6-min walking test (6-MWT) in patients with IPF, we sought to assess the relationship between distance walked and desaturation during this test and pulmonary function tests (PFTs). We also evaluate the prognostic value of 6-MWT in comparison with PFTs at baseline and during follow-up. Methods: The clinical data of 44 patients with IPF were retrospectively analysed. Twenty-nine patients had an additional evaluation after 12 month of follow-up. Results: Distance walked in 6 min was independently related to mortality by multivariate analysis. Patients walking less then 212 m had a significantly lower survival than those walking farther, assessed by Kaplan-Meier survival curves (log-rank test, p < 0.036). During a mean follow-up period of 19.8 months (range 3.2-46.4), 11 patients died of causes related to disease. Changes in meters walked at 12 months evaluation were also predictive of survival (p = 0.05). Conclusions: These results confirm that in IPF distance walked in 6 min is independent associated with mortality

Prevalence of severe asthma according to the drug regulatory agency perspective: An Italian experience

Severe asthma prevalenc

Precision Medicine in Targeted Therapies for Severe Asthma: Is There Any Place for "omics" Technology?

According to the current guidelines, severe asthma still represents a controversial topic in terms of definition and management. The introduction of novel biological therapies as a treatment option for severe asthmatic patients paved the way to a personalized approach, which aims at matching the appropriate therapy with the different asthma phenotypes. Traditional asthma phenotypes have been decomposing by an increasing number of asthma subclasses based on functional and physiopathological mechanisms. This is possible thanks to the development and application of different omics technologies. The new asthma classification patterns, particularly concerning severe asthma, include an increasing number of endotypes that have been identified using new omics technologies. The identification of endotypes provides new opportunities for the management of asthma symptoms, but this implies that biological therapies which target inflammatory mediators in the frame of specific patterns of inflammation should be developed. However, the pathway leading to a precision approach in asthma treatment is still at its beginning. The aim of this review is providing a synthetic overview of the current asthma management, with a particular focus on severe asthma, in the light of phenotype and endotype approach, and summarizing the current knowledge about "omics" science and their therapeutic relevance in the field of bronchial asthma

Towards precision medicine: The application of omics technologies in asthma management

Asthma is a chronic obstructive respiratory disease characterised by bronchial inflammation. Its biological and clinical features have been widely explored and a number of pharmacological treatments are currently available. Currently several aspects of asthma pathophysiological background remain unclear, and this is represent a limitation for the traditional asthma phenotype approach. In this scenario, the identification of new molecular and clinical biomarkers may be helpful in order to better understand the disease, define specific diagnostic tools and highlight relevant novel targets for pharmacological treatments. Omics technologies offer innovative research tools for addressing the above mentioned goals. However, there is still a lot to do both in the fields of basic research and in the clinical application. Recently, genome-wide association studies, microRNAs and proteomics are contributing to enrich the available data for the identification of new asthma biomarkers. A precise approach to the patient with asthma, particularly with severe uncontrolled asthma, requires new and specific therapeutic targets, but also proper tools able to drive the clinician in tailoring the treatment. On the other hand, there is a need of predictors to treatment's response, particularly in the field of biological drugs, whose sustainability implies a correct and precise selection of the patients. Translating acquired omics knowledge in clinical practice may address the unmet needs described above, but large-scale studies are required in order to confirm their relevance and effectiveness in daily practice. Thus in our opinion the application of omics is still lagging in the real-life setting

Drift and Equilibrium Selection with Human and Computer Players

The theory of drift (Binmore and Samuelson 1999) concerns equilibrium selection in which second-order disturbances may have first-order effects in the emergence of one equilibrium over the other. We provided experimental evidence with human players supporting the model in Caminati, Innocenti and Ricciuti (2006). In this paper we test it with conditioning by computer players. When computers are removed and humans are matched against each other, the comparative static properties of the model are confirmed

Use of complementary medicine among patients with allergic rhinitis: an Italian nationwide survey.

Background: A growing use of complementary alternative medicine (CAM) has been found in Europe as well in Italy for chronic diseases, including the allergic rhinitis. The study aims at investigating the prevalence and the pattern of use of CAM amongst patient with allergic rhinitis. Methods: A 12-item questionnaire was developed by a panel of experts and administered to patients with moderate/severe allergic rhinitis consecutively referring during the study time-frame to seven allergy clinics placed all around Italy. The items covered several topics including reason for choosing CAM, its clinical efficacy, schedule of treatment, costs, type of therapy. Results: Overall 359 questionnaires were analysed. 20% of patients declared CAM use. A significant correlation between the use of CAM and female sex (p\u2009<\u20090.01) and with a higher level of education (p\u2009<\u20090.01) was observed. CAM users were adults (36% in the range between 20 and 40 years and 32% between 41 and 60 years). Youngsters (<\u200920 years) (7%) and elderly (>\u200960) (25%) less frequently used CAM.The most used type of CAM was homoeopathy (77% of patients). 60% of users would recommend CAM despite a poor clinical efficacy according to 67% of them. Conclusions: Although no evidence supports CAM efficacy and safety, the number of patients who relies on it is not negligible. As allergic rhinitis is not a trivial disease, the use of CAM as the only treatment for it should be discouraged at any level, but by general practitioner and specialist in particular

Lung cryobiopsy for the diagnosis of interstitial lung diseases: A series contribution to a debated procedure

Introduction: Transbronchial cryobiopsy is an alternative to surgical biopsy for the diagnosis of fibrosing interstitial lung diseases, although the role of this relatively new method is rather controversial. Aim of this study is to evaluate the diagnostic performance and the safety of transbronchial cryobiopsy in patients with fibrosing interstitial lung disease. Materials and methods: The population in this study included patients with interstitial lung diseases who underwent cryobiopsy from May 2015 to May 2018 at the Division of Pneumology of San Giuseppe Hospital in Milan and who were retrospectively studied. All cryobiopsy procedures were performed under fluoroscopic guidance using a flexible video bronchoscope and an endobronchial blocking system in the operating room with patients under general anaesthesia. The diagnostic performance and safety of the procedure were assessed. The main complications evaluated were endobronchial bleeding and pneumothorax. All cases were studied with a multidisciplinary approach, before and after cryobiopsy. Results: Seventy-three patients were admitted to this study. A specific diagnosis was reached in 64 cases, with a diagnostic sensitivity of 88%; 5 cases (7%) were considered inadequate, 4 cases (5%) were found to be non-diagnostic. Only one major bleeding event occurred (1.4%), while 14 patients (19%) experienced mild/moderate bleeding events while undergoing bronchoscopy; 8 cases of pneumothorax (10.9%) were reported, of which 2 (2.7%) required surgical drainage. Conclusions: When performed under safe conditions and in an experienced center, cryobiopsy is a procedure with limited complications having a high diagnostic yield in fibrotic interstitial lung disease