Driving Co-Created Value Through Local Tourism Srvice Systems (LTSS) in Tourism Sector

Purpose – Our purpose is to qualify Local Tourism Area (LTA) as Local Tourism Service System (LTSS), glocal network for value co-creation and equifinality for stakeholders. We identify the conditions and the critical aspects useful for the start-up and the development of a network characterized by a strong international competitiveness. Methodology/approach – Our methodology integrates Service Science Management and Engineering and Viable Systems Approach. SSME is useful for qualifying a Service System; VSA is helpful to interpret tourism territories as Systems. SSME&VSA highlights Structural Variety and Systems Relationship that qualify a LTSS as a long lasting network. Findings – This work provides a general cognitive scheme useful for interpreting LTA as LTSS. So, we can consider a new managing perspective and new ways for developing local service systems according to a governance process based on information sharing, consonance of interpretative patterns and resonance of value categories. Practical implications – Our perspective induces new way of thinking about local systems: territory is not a simply “product” - as static views suggest - but a “service” according to a dynamic view. So, we can see how government guides the development of LTS ensuring distinctive brand destination and place reputation in tourism market. Originality/value – Our paper offers a schema for directing decision makers according to LTA as a LTSS. In the next future, the qualification of the LTSS could be useful to generate a method for measuring the drivers of our model, according to the harmonization among the different governance and the improving reputation of entire servic

A VSA Communication Model for Service Systems Governance.

This paper proposes a conceptual framework for governance and management of the decision making process for corporate communication. The aim is to address a gap in the literature in that to date, by adopting some basic assumptions from Viable Systems Approach, integrated with Service Science perspective, in order to identify communication resources, the nature (static and dynamic) of the corporate communication activities, and “engineering” communication process. Parsons’ sociological approach, with reference to the classification of organisational decisions (policy, allocation and coordination) results fundamental to contextualise this approach to the decision-making within corporate communication function/departmen

The Addition of Venetoclax to Induction Chemotherapy in No Low-Risk AML Patients: A Propensity Score-Matched Analysis of the Gimema AML1718 and AML1310 Trials

Venetoclax combined with intensive chemotherapy proved to be safe with promising activity in fit patients with no-low-risk newly diagnosed acute myeloid leukemia (AML), as demonstrated also by an intermediate analysis of the GIMEMA AML1718 trial (NCT03455504). The latter trial, still ongoing, is based on the administration of venetoclax-FLAI to intermediate/high-risk ELN2017 AML and produced a complete remission (CR) rate of 84%, a minimal residual disease (MRD)-negativity rate of 74% and a 12-month Overall Survival (OS) and disease-free survival (DFS) of 75.7% (95%CI: 64.1%, 89.5%) and 80.7% (95%CI: 67.9%, 95.9%), respectively. In order to evaluate the actual advantage of the addition of venetoclax to chemotherapy, the GIMEMA AML1718 was matched to AML1310, which entailed a "3+7"-like induction and a risk-adapted, MRD-directed post-remission transplant allocation (NCT01452646, Venditti et al - Blood 2019). To generate a reliable comparison, AML1718 and AML1310 were matched by using a propensity score and then compared in terms of CR achievement, MRD-negativity and survival outcomes. Patient-level data from GIMEMA AML1718 (n=57) and AML1310 (N=445) with ELN2017 risk classification available were used to conduct a propensity score matching analysis, widely used for reducing the effects of confounding when estimating the effects of treatment on outcomes. Conditional on the propensity score, the distribution of measured variables is expected to be the same in treated (i.e. AML1718) and control (i.e. AML1310) subjects. In the present propensity score model, we included the following variables: age at diagnosis, gender, ELN2017 risk classification and transplant. Different methods for matching were attempted, including 1:1 nearest neighbor, full-matching, optimal matching (1:2, 1:3 and 1:4) and 1:2 genetic matching. The methods employed for assessing balancing were: i) Standardized Mean Difference - Love plot, ii) Empirical cumulative density function, iii) Variance ratio, iv) Empirical QQ-plot. Weights were calculated with probit or logit regression models according to the propensity score method used. Weights obtained from full-matching were used to adjust outcomes (CR, MRD negativity and survival outcomes). No patients were dropped in the full-matching process. A standardized bias score less than 0.25 was used as a criterion for adequate balancing. We used balance tables and Love plots to assess for covariate balance before and after matching. Survival curves were compared by Log-rank test and Restricted Mean Survival Time (RMST) at 12 months. AML1718 and AML1310 cohorts differed in terms of age (median: 54 vs 49 years, p=0.003) and risk category (p< .0001) - since the low risk was not represented in AML1718 trial - and female sex (35% vs 48%, p=0.069), though to a lesser extent. Contrariwise, the percentage of transplanted patients was comparable before matching (49% vs 49%, p=0.96). Being more recent, AML1718 median follow-up was shorter than AML1310 (10.5 vs 75.8 months). Full-matching, 1:2 optimal matching and 1:2 genetic matching produced the best balancing. Table 1 shows the results of the analysis for the unmatched and matched data. After balancing, according to all matching methods, the CR rate observed in the AML1718 was significantly higher than AML1310, as well as MRD-negativity rate. Comparing survival outcomes at 12 months, emerged that, upon matching, OS and DFS estimates of the AML1718 were higher than those of AML1310, though a slight statistical significance was reached only with the optimal matching on DFS (p=0.042). This result was confirmed by a statistically significant difference between the two RMST at 12 months (p=0.036). Despite this, a longer AML1718 follow-up is needed to provide a robust comparison between the two protocols. Our propensity-score analysis showed that combining venetoclax with chemotherapy in newly diagnosed AML patients resulted in improved outcomes in terms of CR rate and MRD-negativity: these achievements are crucial to allow transition to allogenic transplantation in first remission. With regards to survival outcomes, a solid conclusion will be drawn when a longer AML1718 follow-up is available. These preliminary results highlight the incremental benefit of venetoclax added to intensive induction chemotherapy and paves the way to novel combination regimens based on venetoclax

Screening policies, preventive measures and in-hospital infection of COVID-19 in global surgical practices

Background: In a surgical setting, COVID-19 patients may trigger in-hospital outbreaks and have worse postoperative outcomes. Despite these risks, there have been no consistent statements on surgical guidelines regarding the perioperative screening or management of COVID-19 patients, and we do not have objective global data that describe the current conditions surrounding this issue. This study aimed to clarify the current global surgical practice including COVID-19 screening, preventive measures and in-hospital infection under the COVID-19 pandemic, and to clarify the international gaps on infection control policies among countries worldwide. Methods: During April 2-8, 2020, a cross-sectional online survey on surgical practice was distributed to surgeons worldwide through international surgical societies, social media and personal contacts. Main outcome and measures included preventive measures and screening policies of COVID-19 in surgical practice and centers' experiences of in-hospital COVID-19 infection. Data were analyzed by country's cumulative deaths number by April 8, 2020 (high risk, >5000; intermediate risk, 100-5000; low risk, <100). Results: A total of 936 centers in 71 countries responded to the survey (high risk, 330 centers; intermediate risk, 242 centers; low risk, 364 centers). In the majority (71.9%) of the centers, local guidelines recommended preoperative testing based on symptoms or suspicious radiologic findings. Universal testing for every surgical patient was recommended in only 18.4% of the centers. In-hospital COVID-19 infection was reported from 31.5% of the centers, with higher rates in higher risk countries (high risk, 53.6%; intermediate risk, 26.4%; low risk, 14.8%; P < 0.001). Of the 295 centers that experienced in-hospital COVID-19 infection, 122 (41.4%) failed to trace it and 58 (19.7%) reported the infection originating from asymptomatic patients/staff members. Higher risk countries adopted more preventive measures including universal testing, routine testing of hospital staff and use of dedicated personal protective equipment in operation theatres, but there were remarkable discrepancies across the countries. Conclusions: This large international survey captured the global surgical practice under the COVID-19 pandemic and highlighted the insufficient preoperative screening of COVID-19 in the current surgical practice. More intensive screening programs will be necessary particularly in severely affected countries/institutions

Italian Physicians' Perceptions about the Role of Asciminib in Later Lines Chronic Myeloid Leukemia in Clinical Practice: A GIMEMA Survey

Unmet needs remain in later lines chronic myeloid leukemia (CML): the response rate and the overall survival of resistant patients in the chronic phase who changed a second-generation TKI in the second line with another TKI with similar action are usually poor, while the off-target toxicities and the potential development of mutations increase. The recent approval of asciminib, a STAMP inhibitor, in the third line, has the potential to soon change the therapeutic algorithm for this subset of patients. Here, we report the results of a GIMEMA survey assessing the number of patients currently treated in the third line in Italy, the current approach in later lines by Italian physicians, and the future role of this drug according to the reason to switch to asciminib (resistance and/or intolerance), as well as the perceptions about the future position of this agent

P495: UNLOCKING THE POTENTIAL OF SYNTHETIC PATIENTS FOR ACCELERATING CLINICAL TRIALS: RESULTS OF THE FIRST GIMEMA EXPERIENCE

Background: Artificial intelligence is contributing to improve different medicine areas including clinical trial design. One field that holds a great potential is represented by the use of digital data as an alternative to real ones. The generation of a virtual cohort of patients might be advantageous since an artificial group of patients resembles the real dataset in all the key features but it does not include any identifiable real-patient data, tackling - by a privacy standpoint – the “burden” of collecting data subjects’ consent as well as the shortcomings of common anonymization techniques. Aims: To test the feasibility of this approach and evaluate its potential in clinical trial design, we built an in-silico cohort based on the large dataset of patients enrolled in the GIMEMA AML1310 study (Venditti et al. 2019), which entailed a “3 + 7”-like induction and a risk-adapted, MRD-directed post-remission transplant allocation. Methods: To create the synthetic cohort of patients, a machine learning generative model was constructed from the real individual-level data of the AML1310 study, capturing its patterns and statistical properties. AML1310 enrolled 500 patients (median age 49 years old) in 55 GIMEMA Institutions. All patients were NCCN2009 risk classified and analyzed by morphology, cytogenetics, molecular biology and multiparametric flow cytometry. The subset of 445 patients with ELN2017 risk classification available was used. To this purpose, the R package “synthpop” was used considering a parametric method: for binary data the logistic regression, for a factor with > 2 levels the polytomous logistic regression, for an ordered factor with > 2 levels the ordered polytomous logistic regression. For time to event variables the classification and regression trees method was used. Next, we verified the adherence of the virtual cohort to the original one in terms of age, gender, PS, WBC count, FLT3 and NPM1 mutations, risk category, CR achievement, MRD, transplant rate. Virtual and real cohorts were also compared in terms of survival outcomes. Results: By using the real-patient dataset from the AML1310 trial, a virtual cohort of 850 patients, named synthAML1310, was generated. By comparing the two cohorts, we observed that the clinico-biological characteristics and response evaluations (CR and MRD rates) did not differ significantly. Moreover, as depicted in Figure 1, the curves of OS and DFS were superimposable. Indeed, at 2 years, OS was 57% (52.5%-61.9%) in the original and 59.1% (55.9%-62.6%) in the synthAML1310 cohort. DFS was 55.1% (49.8%-60.9%) in the original and 55.1% (51.3%-59.2%) in the synthetic cohort. Summary/Conclusion: These results demonstrate the success of this approach in producing a virtual dataset that perfectly mimics the original and that, from a “privacy by design” perspective, minimizes the risk of re-identification of patients. Mirroring an AML population treated with a conventional chemotherapeutic approach, synthAML1310 is suitable to represent the control group when testing novel innovative treatments, most likely in an in-silico randomized trial, but also in other settings like propensity score matching analyses in observational studies. Shifting to an in-silico trial would overcome the challenges of randomized trials and it would be beneficial also for patients. since, they would receive only the experimental treatment without being exposed to the “less active“ therapy, thus limiting treatment failures and toxicity. Also, enrolment and the attainment of final results would be faster

Screening policies, preventive measures and in-hospital infection of COVID-19 in global surgical practices

none14siThis research was funded in part by the European Society of Degenerative Disease. The study was registered with an analysis plan on ClinicalTrials.gov (NCT04344197).Background In a surgical setting, COVID-19 patients may trigger in-hospital outbreaks and have worse postoperative outcomes. Despite these risks, there have been no consistent statements on surgical guidelines regarding the perioperative screening or management of COVID-19 patients, and we do not have objective global data that describe the current conditions surrounding this issue. This study aimed to clarify the current global surgical practice including COVID-19 screening, preventive measures and in-hospital infection under the COVID-19 pandemic, and to clarify the international gaps on infection control policies among countries worldwide.Methods During April 2-8, 2020, a cross-sectional online survey on surgical practice was distributed to surgeons worldwide through international surgical societies, social media and personal contacts. Main outcome and measures included preventive measures and screening policies of COVID-19 in surgical practice and centers' experiences of in-hospital COVID-19 infection. Data were analyzed by country's cumulative deaths number by April 8, 2020 (high risk, >5000; intermediate risk, 100-5000; low risk, <100).Results A total of 936 centers in 71 countries responded to the survey (high risk, 330 centers; intermediate risk, 242 centers; low risk, 364 centers). In the majority (71.9%) of the centers, local guidelines recommended preoperative testing based on symptoms or suspicious radiologic findings. Universal testing for every surgical patient was recommended in only 18.4% of the centers. In-hospital COVID-19 infection was reported from 31.5% of the centers, with higher rates in higher risk countries (high risk, 53.6%; intermediate risk, 26.4%; low risk, 14.8%; P<0.001). Of the 295 centers that experienced in-hospital COVID-19 infection, 122 (41.4%) failed to trace it and 58 (19.7%) reported the infection originating from asymptomatic patients/staff members. Higher risk countries adopted more preventive measures including universal testing, routine testing of hospital staff and use of dedicated personal protective equipment in operation theatres, but there were remarkable discrepancies across the countries.Conclusions This large international survey captured the global surgical practice under the COVID-19 pandemic and highlighted the insufficient preoperative screening of COVID-19 in the current surgical practice. More intensive screening programs will be necessary particularly in severely affected countries/institutions.openBellato, Vittoria; Konishi, Tsuyoshi; Pellino, Gianluca; An, Yongbo; Piciocchi, Alfonso; Sensi, Bruno; Siragusa, Leandro; Khanna, Krishn; Pirozzi, Brunella Maria; Franceschilli, Marzia; Campanelli, Michela; Efetov, Sergey; Sica, Giuseppe S; Feo, C;Bellato, Vittoria; Konishi, Tsuyoshi; Pellino, Gianluca; An, Yongbo; Piciocchi, Alfonso; Sensi, Bruno; Siragusa, Leandro; Khanna, Krishn; Pirozzi, Brunella Maria; Franceschilli, Marzia; Campanelli, Michela; Efetov, Sergey; Sica, Giuseppe S; Feo,

Clinical relevance of an objective - limit of detection - limit of quantification - based flow cytometry approach for measurable residual disease assessment in acute myeloid leukemia. A post-hoc analysis of the GIMEMA AML1310 trial

Using a multiparametric flow cytometry (MFC) assay, we assessed the predictive power of a threshold calculated applying the criteria of limit of detection (LOD) and limit of quantitation (LOQ) in adult patients affected with Acute Myeloid Leukemia (AML). This was a post-hoc analysis of 261 patients enrolled in the GIMEMA AML1310 prospective trial. According to the protocol design, using the predefined MRD threshold of 0.035% bone marrow residual leukemic cell (RLC) calculated on mononuclear cells, 154 (59%) were negative (MRD<0.035%) and 107 (41%) were positive (MRD≥0.035%). Using LOD and LOQ, we selected the following categories of patients: 1) LODneg if RLC were below LOD (74; 28.4%); 2) LODpos-LOQneg if RLC were between LOD and LOQ (43; 16.5%); and 3) LOQpos if RLC were above LOQ (144; 54.4%). Two-year overall survival (OS) of these 3 categories was 75.4% vs. 79.8% vs. 66.4%, respectively (p=0.1197). Due to superimposable outcome, LODneg and LODpos-LOQneg categories were combined. Two-year OS of LODneg/LODpos- LOQneg patients was 77.0% versus 66.4% of LOQpos individuals (P=0.043). Such a figure was challenged in multivariate analysis (p=0.048, HR 0.628, 95% CI 0.396-0.997) that confirmed the independent role of LOD-LOQ approach in influencing OS. In the AML1310 protocol, using the threshold of 0.035%, 2-year OS of MRD<0.035% and MRD≥0.035% patients was 74.5% vs. 66.4%, respectively (p=0.3521). In conclusion, the use of LOD-LOQ method results in a more sensitive detection of MRD that, in turn, translates in a more accurate recognition of patients with different outcome