Performance analysis of indicators of chaos for nonlinear dynamical systems.

The efficient detection of chaotic behavior in orbits of a complex dynamical system is an active domain of research. Several indicators have been proposed, and new ones have recently been developed in view of improving the performance of chaos detection by means of numerical simulations. The challenge is to predict chaotic behavior based on the analysis of orbits of limited length. In this paper the performance analysis of past and recent indicators of chaos, in terms of predictive power, is carried out in detail using the dynamical system characterized by a symplectic Hénon-like cubic polynomial map.

Exploring disease perception in Behçet's syndrome: combining a quantitative and a qualitative study based on a narrative medicine approach.

BACKGROUND: Behçet Syndrome (BS) has a significant psychological and social impact on patients, caregivers and families. The present study aims at exploring disease perception in BS patients, using both a co-designed survey and the narrative medicine (NM) approach. METHODS: An ad-hoc questionnaire was co-designed by clinicians expert in BS, BS patients and caregivers and BS adult patients were invited to answer the online questionnaires. Cluster analysis was used to analyse data from the survey and to identify groups of patients with diverse disease perception. To further explore real-life perspectives, the stories of illness of a smaller group of adult BS patients were anonymously collected online and analysed by means of text, sentiment and qualitative analysis. RESULTS: Two hundred and seven patients answered the survey and forty-three stories were collected. The cluster analysis highlighted that accepting or not the disease has a strong impact on the daily life, on how BS patients perceive themselves and in terms of hope for the future. The stories revealed that patients often address common issues, such as the long and complex journey faced from the disease onset until the BS diagnosis, which was strongly connected to the concept of time and perceived as an exhausting period of their lives. CONCLUSION: To our knowledge, this is the first study that addressed disease perception also applying the NM principles in BS. The current perception that BS patients have of their disease should encourage the BS scientific and patient community in joining forces in order to improve the journey of BS patients.

Drug-eluting Microspheres Compared to Conventional Transarterial Chemoembolization as First Line Treatment for Unresectable Hepatocellular Carcinoma: A Single-center Retrospective Cost-utility Analysis.

PURPOSE: To assess the cost-utility of initial treatment with drug-eluting microspheres (DEM) transarterial chemoembolization (TACE) versus conventional (C)-TACE in patients with hepatocellular carcinoma considering the perspective of a Local Healthcare Authority in Italy. MATERIALS AND METHODS: The economic evaluation is based on a retrospective single-center study and individual patients' data whose details have been previously reported. The impact of initial treatment with DEM-TACE or C-TACE on disease progression, mortality, and direct health costs over a lifetime horizon were simulated and compared in terms of incremental cost-utility ratio expressed as costs per quality adjusted life years (QALY). Costs included direct health costs related to the first chemoembolization procedure and all subsequent follow-up costs associated with health care resources used for disease management. Probabilistic (PSA) sensitivity analysis was used to assess the robustness of the results. RESULTS: A total of 101 patients in each treatment group were considered. All over the time-horizon median costs were €3,145.14 and €2,158.32 in the DEM-TACE and C-TACE group, respectively (p < 0.001); while mean costs were € 24,619 and € 17,001, respectively (p < 0.001). The ICUR was 6,461.86 €/QALY when using median costs derived from the study population as input for the health-economic evaluation and 49,932.15 €/QALY when the mean costs were considered. Results from PSA highlighted that using median costs DEM-TACE was always cost-effective, while using mean costs, it was preferable only 24.7% of times. CONCLUSIONS: The higher prices of DEMs are counterbalanced by the positive impact on QALY.

Late chronotypes, late mealtimes. Chrononutrition and sleep habits during the COVID-19 lockdown in Italy.

The emerging field of chrononutrition provides useful information on how we manage food intake across the day. The COVID-19 emergency, and the corresponding restrictive measures, produced an unprecedented change in individual daily rhythms, possibly including the distribution of mealtimes. Designed as a cross-sectional study based on an online survey, this study aims to assess the chrononutrition profiles (Chrononutrition Profile Questionnaire, CP-Q) in a sample of 1298 Italian participants, during the first COVID-19 lockdown, and to explore the relationship with chronotype (reduced Morningness-Eveningness Questionnaire, rMEQ), sleep quality (Pittsburgh Sleep Quality Index, PSQI) and socio-demographics. Our findings confirm a change in eating habits for 58% of participants, in terms of mealtimes or content of meals. Being an evening chronotype and experiencing poor sleep imply a higher likelihood of changing eating habits, including a delay in the timing of meals. Also, under these unprecedented circumstances, we report that the timing of breakfast is a valuable proxy capable of estimating the chronotype. From a public health perspective, the adoption of this straightforward and low-cost proxy of chronotype might help in the early detection of vulnerable subgroups in the general population, eventually useful during prolonged stressful conditions, as the one caused by COVID-19 pandemic.

Poor sleep quality and unhealthy lifestyle during the lockdown: an Italian study.

BACKGROUND: The lockdown measure implemented to face the 2019 Coronavirus Disease (COVID-19) first wave deeply modified the lifestyle of the Italian population. Despite its efficacy in limiting the number of infections, forced home confinement was paralleled by sleep/wake cycle disruptions, psychological distress and maladaptive coping strategies (i.e., unhealthy behaviours, such as tobacco and alcohol consumption). Under these unprecedented stress conditions, we explored a possible association between poor sleep quality and increased likelihood of engaging in an unhealthy lifestyle. METHODS: A cross-sectional study was conducted by disseminating an online survey via social networks and e-mail. We collected information on demographics, COVID-19-related data, sleep quality, chronotype, circadian misalignment, and lifestyle before and during the lockdown (i.e., consumption of cigarettes, alcoholic beverages, coffee, hypnotics, comfort food and fresh food; practice of physical activity). A global healthiness score was computed to assess participants' modifications in lifestyle since the beginning of the lockdown. RESULTS: 1297 respondents were included in the study: 414 (31.9%) from Northern Italy, 723 (55.8%) from Central Italy, 160 (12.3%) from Southern Italy. The following variables were found to be significant predictors of the adoption of an unhealthy lifestyle since the beginning of the lockdown: poor sleep quality, high BMI and considering the measures adopted by the government to fight the pandemic as excessive. Living in Northern Italy, instead, was associated with healthier habits compared to living in Central Italy. CONCLUSIONS: Poor sleepers may represent the share of the general population who paid the highest price for social isolation. Further investigations are required to explore the role of sleep quality assessment in the identification of individuals vulnerable to unhealthy behaviours under stressful conditions.

A systematic literature review of existing tools used to assess medication adherence in connective tissue diseases: the state of the art for the future development of co-designed measurement tools.

Lack of medication adherence is frequent in chronic connective tissue diseases and is associated with poorer health outcomes, low quality of life and economic loss. This research is based on a systematic literature search and aims to identify the surveys and tools used for the assessment of medication adherence in patients with connective tissue diseases (CTDs) and in particular the tools co-designed with patients. A systematic literature review was performed in PubMed and Embase databases searching for studies concerning the application of surveys or tools designed for medication adherence assessment. A specific analysis was also performed to identify which of these existing tools were developed in co-design with patients affected by CTDs. 1958 references were identified, and 31 studies were finally included. Systemic lupus erythematosus was the most investigated disease, followed by the Behçet's disease. The tools used to assess adherence in CTDs were, in most cases, valid and useful. However, the results showed a certain degree of heterogeneity among the studies and the medication adherence assessment and measurement tools adopted, which were mostly based on selfreported questionnaire. No co-designed tools with patients were found. Low- and non-adherence were explored in some CTDs with valid and useful tools, while other CTDs still need to be assessed. Therefore, more efforts should be made to better understand the specific reasons for the low- and non-adherence in CTDs patients.

Propagation of rays in 2D and 3D waveguides: A stability analysis with Lyapunov and reversibility fast indicators.

Propagation of rays in 2D and 3D corrugated waveguides is performed in the general framework of stability indicators. The analysis of stability is based on the Lyapunov and reversibility error. It is found that the error growth follows a power law for regular orbits and an exponential law for chaotic orbits. A relation with the Shannon channel capacity is devised and an approximate scaling law found for the capacity increase with the corrugation depth.

Sleep quality mediates the effect of chronotype on resilience in the time of COVID-19.

This study aimed to explore the relationship between chronotype and resilience, sleep quality, and post-traumatic stress reactions during the first COVID-19 lockdown in Italy. An online survey was distributed through social networks during forced home confinement, collecting data from1298 participants of 19 different Italian regions. Chronotype was evaluated using the reduced version of the Morningness/Eveningness Questionnaire (rMEQ); sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI); resilience levels were measured by the 10-item version of the Connor-Davidson Resilience Scale (CD-RISC10); post-traumatic stress reactions were assessed by the 6-item version of the Impact of Event Scale (IES6). Resilience and sleep quality were significantly lower in the evening compared to non-evening types, as well as in females as compared to males. Moreover, resilience was negatively correlated with post-traumatic stress reactions and positively correlated with sleep quality. A negative correlation was also reported between sleep quality and post-traumatic stress reactions. Sleep quality was identified as a possible mediator between chronotype and resilience, and between resilience and post-traumatic stress reactions, after controlling for age and sex. These findings provide new insights into the role of chronotype in adapting to continuous stressful situations. Sleep quality seems to mediate the causal path between the antecedents of resilience and the development of trauma. Further research is needed to explore the suitability of primary interventions based on chronobiology and sleep hygiene to mitigate the impact of pandemic-related home confinement measures on mental health among the general population.

The cost-effectiveness of transcatheter aortic valve implantation: exploring the Italian National Health System perspective and different patient risk groups.

OBJECTIVES: To assess the cost-effectiveness (CE) of transcatheter aortic valve implantation (TAVI) in Italy, considering patient groups with different surgical risk. METHODS: A Markov model with a 1-month cycle length, comprising eight different health states, defined by the New York Heart Association functional classes (NYHA I-IV), with and without stroke plus death, was used to estimate the CE of TAVI for intermediate-, high-risk and inoperable patients considering surgical aortic valve replacement or medical treatment as comparators according to the patient group. The Italian National Health System perspective and 15-year time horizon were considered. In the base-case analysis, effectiveness data were retrieved from published efficacy data and total direct costs (euros) were estimated from national tariffs. A scenario analysis considering a micro-costing approach to estimate procedural costs was also considered. The incremental cost-effectiveness ratio (ICER) was expressed both in terms of costs per life years gained (LYG) and costs per quality adjusted life years (QALY). All outcomes and costs were discounted at 3% per annum. Univariate and probabilistic sensitivity analyses (PSA) were performed to assess robustness of results. RESULTS: Over a 15-year time horizon, the higher acquisition costs for TAVI were partially offset in all risk groups because of its effectiveness and safety profile. ICERs were €8338/QALY, €11,209/QALY and €10,133/QALY, respectively, for intermediate-, high-risk and inoperable patients. ICER values were slightly higher in the scenario analysis. PSA suggested consistency of results. CONCLUSIONS: TAVI would be considered cost-effective at frequently cited willingness-to-pay thresholds; further studies could clarify the CE of TAVI in real-life scenarios.

Prostanoids in scleroderma microangiopathy: clinical and pharmacoeconomic comparison between two intravenous regimens.

Objectives: Intravenous iloprost (ILO) has widely demonstrated its effectiveness and safety in systemic sclerosis (SSc) patients. Unfortunately, there is no clear consent about dosage, duration, frequency, and infusion modality. The aim of this study was to compare two different therapeutic schemes in the same cohort of consecutive SSc subjects, evaluating differences in terms of effectiveness [digital ulcer (DU) outcome], safety, and direct healthcare costs.Method: This was a retrospective observational study of 47 patients classified with SSc treated with intravenous ILO for severe Raynaud's phenomenon and/or DUs. Two regimens were compared: a continuous inpatient scheme and a daily outpatient scheme. Demographics and clinical data, concomitant therapies, adverse events, and data on resource use and costs were collected.Results: The number of DUs rose slightly with the switch from the continuous to the daily scheme (0.61 ± 1.2 vs 1.1 ± 1.7). Moreover, in the daily scheme there was an increase in the number of therapeutic cycles (2.4 ± 0.7 vs 4.71 ± 1.4, p < 0.001) and an increase in patients treated with other vasoactive drugs. There was a reduction in ILO tolerability and more than half of the patients suspended the treatment. Five patients required hospitalization for severe and refractory DUs in the daily scheme. Moreover, the costs of the two treatments were comparable [median 7174 (range 2748-18 524) EUR vs 6284 (3232-22 706) EUR, p = 0.712].Conclusion: Treatment with a daily scheme of ILO is characterized by worse tolerability and a higher dropout rate compared to a low-flow regimen, with similar costs. We suggest that a low-flow continuous therapeutic scheme is preferable in SSc patients.

Translation, cultural adaptation and validation of the Systemic Lupus Erythematosus Activity Questionnaire (SLAQ) in a cohort of Italian systemic lupus erythematosus patients.

Introduction The Systemic Lupus Erythematosus Activity Questionnaire (SLAQ) is a patient-reported instrument for the assessment of disease activity in systemic lupus erythematosus (SLE). The aims of the present study are translation, cultural adaptation and validation of an Italian version: the SLAQit. Methods The process of translation and cultural adaptation followed published guidelines. SLAQit was pretested in a group of 35 SLE patients to evaluate acceptability, comprehension and feasibility. Internal consistency, test-retest validity and external validity were tested on consecutive SLE patients attending the clinic. Results In total, 135 SLE patients were enrolled in this study. The pilot test provided a 99.9% response rate and demonstrated feasibility and comprehensibility of the questionnaire. A good internal consistency was found among the three components of the score (SLAQ score, numerical rating scale (NRS), patient global assessment question (PGA); α = 0.79). SLAQit showed very high reliability (test-retest α > 0.8). NRS and PGA showed a strong positive correlation with both Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) ( p = 0.002 and p < 0.001, respectively) and European Consensus Lupus Measurement (ECLAM) scores ( p = 0.01 and p < 0.001, respectively), while the SLAQ score did not. A significant agreement was observed between the physician's intention to treat and both the NRS and PGA scores, while no significant association was reported with the SLAQ score. Conclusions SLAQit was demonstrated to be a reliable and valid instrument for self-assessment of disease activity in SLE patients.

Delayed diagnosis and treatment of tuberculosis in HIV+ patients in Mozambique: A cost-effectiveness analysis of screening protocols based on four symptom screening, smear microscopy, urine LAM test and Xpert MTB/RIF.

BACKGROUND: Tuberculosis (TB) represents the ninth leading cause of death worldwide. In 2016 are estimated 1.3 million TB deaths among HIV negative people and an additional 374,000 deaths among HIV positive people. In 2016 are estimated 1.4 million new cases of TB in people living with HIV (PLHIV), 74% of whom were living in Africa. In light of these data, the reduction of mortality caused by TB in PLHIV is strongly required specially in low-income countries as Mozambique. According to international guidelines, the initial TB screening in HIV+ patients should be done with the four symptoms screening (4SS: fever, current cough, night sweats and weight loss). The diagnostic test more used in resource-limited countries is smear microscopy (SMEAR). World Health Organization (WHO) recommended Lateral Flow urine LipoArabinoMannan assay (LF-LAM) in immunocompromised patients; in 2010 WHO endorsed the use of Xpert Mycobacterium Tuberculosis/Rifampicin (MTB/RIF) test for rapid TB diagnosis but the assay is not used as screening test in all HIV+ patients irrespectively of symptoms due to cost and logistical barriers. The paper aims to evaluate the cost-effectiveness of three screening protocols: standard (4SS and SMEAR in positive patients to 4SS); MTB/RIF; LF-LAM / MTB/RIF. METHODS: We developed a model to assess the cost-effectiveness of the MTB/RIF protocol versus the common standard and LF-LAM / MTB/RIF protocol. The model considered a sample of 1,000 HIV+ antiretroviral treatment naïve patients in Mozambique. We evaluated disability-adjusted life year (DALY) averted for each protocol, cost per DALY, and incremental cost-effectiveness ratio (ICER), over 1-year, assuming a national healthcare system perspective. The model considered the delayed diagnosis as the time elapsed between a false negative test and the diagnosis and treatment of TB. Additional health system organization delay is defined as the time interval between positive test and treatment initiation caused by a delay in the delivery of results due organization of services. We conducted a sensitivity analysis on more relevant variables. RESULTS: The MTB/RIF protocol was cost-effective as compared to the standard protocol with an ICER of $56.54 per DALY saved. In a cohort of 1,000 patients MTB/RIF and LF-LAM / MTB/RIF protocol generated 1,281 and 1,254 DALY's saved respectively, with a difference of 174 and 147 DALY respect to the standard protocol. The total cost of MTB/RIF protocol was lower ($92,263) than the standard ($147,226) and the LF-LAM / MTB/RIF ($113,196). Therefore, the cost per DALY saved including new infections due to delayed diagnosis with the standard protocol was $79.06, about 5 fold higher than MTB/RIF and LF-LAM / MTB/RIF protocols. The cost of additional TB infections due to delays in diagnosis plus health system delay seemed the more relevant costs. The low sensibility and sensitivity of the standard protocol led to a high number of false negatives, thus delayed TB diagnoses and treatment lead to the development of newly transmitted TB infections. CONCLUSIONS: Our study shows that the MTB/RIF adoption could lead to an increasing of TB case-finding and a reduction in costs compared with standard and LF-LAM / MTB/RIF protocols.

Cochlear implant in prelingually deafened oralist adults: speech perception outcomes, subjective benefits and quality of life improvement.

The aim of this study is to report our results in a group of prelingually deafened adults, who followed an oralist rehabilitation programme, and submitted to cochlear implant at our institution. We evaluated 30 prelingually deafened adult patients, 18 males and 12 females, median age 35 years, of a group of 36 prelingually deafened adult patients consecutively submitted to unilateral cochlear implantation at the ENT Unit of the University of Pisa. After implantation, patients achieved significant benefits in terms of speech perception skills, including the ability to have telephone conversations in some cases, quality of life and their own perception of disability. According to literature data, the results herein reported are quite variable but generally satisfactory. Procedures other than traditional speech perception measures should be used to evaluate the benefits of cochlear implant in such patients, to compressively evaluate the global benefits, not only in terms of speech perception, but also in terms of quality of life and daily life.

The social cost of rheumatoid arthritis in Italy: the results of an estimation exercise.

The objective of this study is to estimate the mean annual social cost per adult person and the total social cost of rheumatoid arthritis (RA) in Italy. A literature review was performed by searching primary economic studies on adults in order to collect cost data of RA in Italy in the last decade. The review results were merged with data of institutional sources for estimating - following the methodological steps of the cost of illness analysis - the social cost of RA in Italy. The mean annual social cost of RA was € 13,595 per adult patient in Italy. Affecting 259,795 persons, RA determines a social cost of € 3.5 billions in Italy. Non-medical direct cost and indirect cost represent the main cost items (48% and 31%) of the total social cost of RA in Italy. Based on these results, it appears evident that the assessment of the economic burden of RA solely based on direct medical costs evaluation gives a limited view of the phenomenon.

Instrumentation for diagnostics and control of laser-accelerated proton (ion) beams.

Suitable instrumentation for laser-accelerated proton (ion) beams is critical for development of integrated, laser-driven ion accelerator systems. Instrumentation aimed at beam diagnostics and control must be applied to the driving laser pulse, the laser-plasma that forms at the target and the emergent proton (ion) bunch in a correlated way to develop these novel accelerators. This report is a brief overview of established diagnostic techniques and new developments based on material presented at the first workshop on 'Instrumentation for Diagnostics and Control of Laser-accelerated Proton (Ion) Beams' in Abingdon, UK. It includes radiochromic film (RCF), image plates (IP), micro-channel plates (MCP), Thomson spectrometers, prompt inline scintillators, time and space-resolved interferometry (TASRI) and nuclear activation schemes. Repetition-rated instrumentation requirements for target metrology are also addressed.