Impatto dell’epidemia da COVID-19 in Friuli Venezia Giulia: Valutazione dei fattori associati al rischio di decesso mediante l’analisi dei rischi competitivi /Impact of the COVID-19 epidemic in Friuli Venezia Giulia Region (Northern Italy): assessment of factors associated with the risk of death by competing risks analysis

OBJECTIVES: To investigate the role of gender, age, province of residence, and nursing home residency on the risk of death for residents in the Friuli Venezia Giulia (FVG) Region (Northern Italy) tested positive for COVID-19, considering recovery as a competing event. The secondary objective is to describe the impact of the COVID-19 epidemic in FVG and in the Regions of Northern and Central Italy in terms of incidence and mortality compared to the national data. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: Resident population in FVG in the period between 29 February and 25 June 2020. MAIN OUTCOME MEASURES: In order to describe the impact of the COVID-19 outbreak in FVG, in terms of incidence and mortality compared to the national data, the standardized incidence (SIR) and mortality (SMR) ratios and their respective 95 confidence intervals (95CI) were calculated compared to the Italian population for the northern and central Regions of Italy and the autonomous Provinces (PA) of Trento and Bolzano. A retrospective cohort study was conducted on subjects residing in FVG to whom at least one naso-oropharyngeal swab (hereafter, named swab) resulted positive for COVID-19. For each subject included in the cohort, the observation period started with the first positive swab and ended with the first of the following events: Death, recovery or censored, which means that at the end of the observation period the subject was still alive and positive. The cause of death was assigned to COVID-19 if a subject had not yet recovered at the time when the event occurred. Cohort members were considered recovered after two negative consecutive swabs. The sub-hazard ratio (SHR) was estimated by applying the regression model of competing risks by Fine and Gray, in which the event of interest was the death caused by COVID-19 and the competing event was recovery. The explanatory variables included in the multiple models are: Gender, age at the beginning of the observation period, the Province of residence, and nursing home residency

Safety and Efficacy of Subcutaneous Rituximab in Previously Untreated Patients with CD20+ Diffuse Large B-Cell Lymphoma or Follicular Lymphoma: Results from an Italian Phase IIIb Study

Subcutaneous (SC) rituximab may be beneficial in terms of convenience and tolerability, with potentially fewer and less severe administration-related reactions (ARRs) compared to the intravenous (IV) form. This report presents the results of a phase IIIb study conducted in Italy. The study included adult patients with CD20+ DLBCL or FL having received at least one full dose of IV RTX 375 mg/m2 during induction or maintenance. Patients on induction received ≥4 cycles of RTX SC 1400 mg plus standard chemotherapy and FL patients on maintenance received ≥6 cycles of RTX SC. Overall, 159 patients (73 DLBCL, 86 FL) were enrolled: 103 (54 DLBCL, 49 FL) completed induction and 42 patients with FL completed 12 maintenance cycles. ARRs were reported in 10 patients (6.3%), 3 (4.2%) with DLBCL and 7 (8.1%) with FL, all of mild severity, and resolved without dose delay/discontinuation. Treatment-emergent adverse events (TEAEs) and serious adverse events occurred in 41 (25.9%) and 14 patients (8.9%), respectively. Two patients with DLBCL had fatal events: Klebsiella infection (related to rituximab) and septic shock (related to chemotherapy). Neutropenia (14 patients, 8.9%) was the most common treatment-related TEAE. Two patients with DLBCL (2.8%) and 6 with FL (7.0%) discontinued rituximab due to TEAEs. 65.2% and 69.7% of patients with DLBCL and 67.9% and 73.6% of patients with FL had complete response (CR) and CR unconfirmed, respectively. The median time to events (EFS, PFS, and OS) was not estimable due to the low rate of events. At a median follow-up of 29.5 and 47.8 months in patients with DLBCL and FL, respectively, EFS, PFS, and OS were 70.8%, 70.8%, and 80.6% in patients with DLBCL and 77.9%, 77.9%, and 95.3% in patients with FL, respectively. The switch from IV to SC rituximab in patients with DLBCL and FL was associated with low risk of ARRs and satisfactory response in both groups. This trial was registered with NCT01987505

Standardization of incidence rates of mesothelioma in the absence of national standards: sensitivity analysis in a cohort formerly exposed to asbestos

INTRODUCTION: The incidence of mesothelioma in Italy shows wide geographical variation, with the highest incidence rates in Genoa and Friuli Venezia Giulia (FVG). For mesothelioma, national standard incidence rates are not available prior to the calendar year 2006. OBJECTIVES: To estimate the Standardized Incidence rate Ratio (SIR) of mesothelioma in a cohort of former workers undergoing health surveillance because of previous asbestos exposure, when sex-, age-, and calendar year-specific rates of the national standard are not available and the number of expected cases calculated from the regional rates is biased by the size of the study cohort. METHODS: We conducted a sensitivity analysis in a cohort of 2,488 men. We considered every Italian cancer registry available with complete data in the period 1995-2007 (N=14). We calculated, for each year and age group, the corresponding weighted mean rate of 10 registries of North-Italy (Mean W10), the weighted mean rate of all 14 registries available (Mean W14) and considered FVG standard rate. RESULTS: During the period 1995-2007, we observed 25 incident cases of mesothelioma with expected cases that varied between 2.00 (Mean W14) and 2.56 (FVG standard rate), with a SIR of 12.49 (CI95% 8.08-18.48) and 9.76 (CI95% 6.32-14.45) respectively. CONCLUSIONS: Our results show that the use of FVG rates as standard does not lead to significant distortions in the calculation of the expected cases. However, distortion is remarkable in the SIRs estimation. Using a weighted mean standard incidence rate may be a valid alternative for SIR estimate when national standard rates are not available

Stima del rapporto standardizzato di incidenza di mesotelioma in mancanza di tassi standard nazionali:analisi di sensibilità in una coorte di ex esposti ad amianto

7noIntroduzione: L’incidenza di mesotelioma in Italia mostra una forte variazione geografica, con i tassi d’incidenza più elevati per Genova e Friuli Venezia Giulia. Per il mesotelioma non sono disponibili tassi d’incidenza standard nazionali, età, sesso e anno specifici, antecedenti al 2006. Obiettivi: Stimare i Rapporti Standardizzati di Incidenza (SIR) di mesotelioma in una coorte di lavoratori ex-esposti ad amianto sottoposti a sorveglianza sanitaria, in assenza di tassi standard nazionali di riferimento e quando il numero di casi attesi, calcolato sulla base dei tassi regionali, sia distorto dalla dimensione della coorte di studio. Metodi: Abbiamo condotto un’analisi di sensibilità in una coorte di 2.488 uomini considerando tutti i registri tumori italiani disponibili nel periodo 1995-2007 (N=14). Abbiamo calcolato, per ciascuna classe d’età e anno di calendario, il tasso medio ponderato dei 10 registri nel nord Italia (media P10), il tasso medio ponderato dei 14 registri (media P14), e considerato il tasso standard FVG (Tasso FVG). Risultati: Nel periodo 1995-2007 i casi attesi di mesotelioma variavano da 2,00 (media P14) a 2,56 (tasso FVG), con SIR rispettivamente di 12,49 (IC 95% 8,08-18,48) e 9,76 (IC 95% 6,32-14,45). Conclusioni: I risultati evidenziano come il semplice uso dei tassi FVG non comporti distorsioni importanti nel calcolo degli attesi. Al contrario se si considerano i SIR tale distorsione è notevole. Pertanto ne consegue che il tasso d’incidenza medio ponderato quale standard può essere una valida alternativa per il calcolo dei SIR in assenza di tassi standard nazionali.reservedmixedBarbiero, F; Giangreco, M; Pisa, Fe; Negro, C; Bovenzi, M; Rosolen, V; Barbone, FBarbiero, F; Giangreco, M; Pisa, Fe; Negro, Corrado; Bovenzi, Massimo; Rosolen, V; Barbone, F

Mortality in a cohort of asbestos-exposed workers undergoing health surveillance

Background: The coastal area of Friuli Venezia Giulia (FVG) region, north-eastern Italy, was characterized by work activities in which asbestos was used until the early 1990s, particularly in shipbuilding. A public health sur- veillance program (PHSP) for asbestos-exposed workers was established, although limited evidence exists about the efficacy of such programs in reducing disease occurrence and mortality. Objectives: To compare mortality in a cohort of 2,488 men occupationally exposed to asbestos, enrolled in a PHSP in FVG between the early 1990s and 2008, with that of the general population of FVG and Italy. Methods: Standardized Mortality Ratios (SMR), with 95% Con- fidence Interval (95% CI), for all causes, all cancers, lung (LC) and pleural cancer (PC) were estimated in the cohort and in subgroups of workers with the first hire in shipbuilding that caused asbestos exposure (<1974, 1974-1984, 1985-1994). Results: A strong excess in mortality for PC with reference to FVG (SMR=6.87, 95% CI 4.45-10.17) and Italian population (SMR=13.95, 95% CI 9.02-20.64) was observed. For LC, the FVG-based SMR was 1.49 (95% CI 1.17-1.89) and the Italy-based 1.43 (95% CI 1.12-1.81). Mortality among workers with the first hire in shipbuilding before 1974 was high for PC (FVG-based SMR=8.98, 95% CI 5.56-13.75; Italy-based SMR=18.41, 95% CI 11.40-28.17) and for LC (FVG-based SMR =1.60, 95% CI 1.18-2.11; Italy-based SMR=1.54, 95% CI 1.14-2.03). Further, for LC between 1974 and 1984, the FVG-based SMR was 2.45 (95% CI 1.06-4.82), and the Italy-based SMR was 2.33 (95% CI 1.01-4.60). Conclusions: This cohort experienced an excess mortality for pleural and lung cancer, compared with regional and national populations. For lung cancer, the excess was stronger in workers with the first hire in shipbuilding before 1985, suggesting a key role of asbestos exposure

Mortality in a cohort of asbestos-exposed workers undergoing health surveillance

9noBackground: The coastal area of Friuli Venezia Giulia (FVG) region, north-eastern Italy, was characterized by work activities in which asbestos was used until the early 1990s, particularly in shipbuilding. A public health sur- veillance program (PHSP) for asbestos-exposed workers was established, although limited evidence exists about the efficacy of such programs in reducing disease occurrence and mortality. Objectives: To compare mortality in a cohort of 2,488 men occupationally exposed to asbestos, enrolled in a PHSP in FVG between the early 1990s and 2008, with that of the general population of FVG and Italy. Methods: Standardized Mortality Ratios (SMR), with 95% Con- fidence Interval (95% CI), for all causes, all cancers, lung (LC) and pleural cancer (PC) were estimated in the cohort and in subgroups of workers with the first hire in shipbuilding that caused asbestos exposure (<1974, 1974-1984, 1985-1994). Results: A strong excess in mortality for PC with reference to FVG (SMR=6.87, 95% CI 4.45-10.17) and Italian population (SMR=13.95, 95% CI 9.02-20.64) was observed. For LC, the FVG-based SMR was 1.49 (95% CI 1.17-1.89) and the Italy-based 1.43 (95% CI 1.12-1.81). Mortality among workers with the first hire in shipbuilding before 1974 was high for PC (FVG-based SMR=8.98, 95% CI 5.56-13.75; Italy-based SMR=18.41, 95% CI 11.40-28.17) and for LC (FVG-based SMR =1.60, 95% CI 1.18-2.11; Italy-based SMR=1.54, 95% CI 1.14-2.03). Further, for LC between 1974 and 1984, the FVG-based SMR was 2.45 (95% CI 1.06-4.82), and the Italy-based SMR was 2.33 (95% CI 1.01-4.60). Conclusions: This cohort experienced an excess mortality for pleural and lung cancer, compared with regional and national populations. For lung cancer, the excess was stronger in workers with the first hire in shipbuilding before 1985, suggesting a key role of asbestos exposure.reservedmixedFabiano Barbiero, Tina Zanin, Federica Edith Pisa, Anica Casetta, Valentina Rosolen, Manuela Giangreco, Corrado Negro, Massimo Bovenzi, Fabio BarboneFabiano, Barbiero; Tina, Zanin; Federica Edith Pisa, ; Anica, Casetta; Rosolen, Valentina; Manuela, Giangreco; Negro, Corrado; Bovenzi, Massimo; Barbone, Fabi

Outcomes of patients with continuous flow left ventricular assist device undergoing emergency endovascular treatment for atraumatic bleeding

INTRODUCTION: Severe spontaneous bleeding is a significant complication in patients with continuous flow left ventricular assist devices; there is little evidence on endovascular treatment to support its use.MATERIALS AND METHODS: We observed seven patients (five men, two women, age 43-67years) with continuous flow left ventricular assist devices on antiaggregant/coagulant therapy, admitted to our hospital for uncorrectable symptomatic anemia; CT-angiography and diagnostic angiography confirmed the presence of atraumatic arterious bleeding from the gastrointestinal tract (six patients), from the intercostal artery and from the bronchial tree (one patient).RESULTS: All patients where successfully treated via an endovascular approach with superselective embolization of the involved arterial branches with coils and particles.CONCLUSION: Spontaneous atraumatic bleeding is a frequent complication in patients with continuous flow left ventricular assist devices; endovascular treatment represents a promising alternative to the surgical approach as it is less invasive, easily repeatable and associated to a reduced procedural risk

Impact of low-dose computed tomography screening on lung cancer mortality among asbestos-exposed workers

Background: We previously showed that low-dose computed tomography (LDCT) screening in asbestos-exposed workers is effective in detecting lung cancer (LC) at an early stage. Here, we evaluate whether LDCT screening could reduce mortality from LC in such a high-risk population.Methods: Within a cohort of 2433 asbestos-exposed men enrolled in an Occupational Health surveillance programme, we compared mortality between the participants in the ATOM002 study (LDCT-P, N = 926) and contemporary non-participants (LDCT-NP, N = 1507). We estimated standardized mortality ratios for the LDCT-P and LDCT-NP populations using regional and national rates (SMR_FVG and SMR_ITA, respectively). We compared survival for all causes, all neoplasms, LC and malignant neoplasm of pleura (MNP) between LDCT-P and LDCT-NP using Cox proportional hazard models adjusted for age, smoking history, asbestos exposure level and comorbidities.Results: A reduction in mortality from LC was observed in the LDCT-P group compared with regional and national figures (SMR_FVG = 0.55, 95% confidence interval (Cl) 0.24-1.09; SMR_ITA = 0.51, 95% Cl 0.22-1.01); this was not the case for the LDCT-NP group (SMR_FVG = 2.07, 95% CI 1.53-2.73; SMR_ITA = 1.98, 95% CI 1.47-2.61). A strong reduction in LC mortality was observed for the LDCT-P compared with the LDCT-NP [hazard ratio (HR) = 0.41, 95% CI 0.17-0.96]. Mortality was also reduced for all causes (HR = 0.61, 95% CI 0.44-0.84), but not for all neoplasms (HR = 0.97, 95% CI 0.62-1.50) and MNP (HR = 0.86, 95% CI 0.31-2.41) within the LDCT-P population.Conclusions: In our cohort, participation in the LDCT screening study was associated with reduced mortality from LC. This finding supports the use of LDCT in surveillance programmes for asbestos-exposed workers

The submerged dyslexia iceberg: how many school children are not diagnosed? Results from an Italian study.

BACKGROUND: Although dyslexia is one of the most common neurobehavioral disorders affecting children, prevalence is uncertain and available data are scanty and dated. The objective of this study is to evaluate the prevalence of dyslexia in an unselected school population using clearly defined and rigorous diagnostic criteria and methods. METHODS: Cross sectional study. We selected a random cluster sample of 94 fourth grade elementary school classes of Friuli Venezia Giulia, a Region of North Eastern Italy. We carried out three consecutive levels of screening: the first two at school and the last at the Neuropsychiatry Unit of a third level Mother and Child Hospital. The main outcome measure was the prevalence of dyslexia, defined as the number of children positive to the third level of screening divided by the total number of children enrolled. RESULTS: We recruited 1774 children aged 8-10 years, of which 1528 received parents' consent to participate. After applying exclusion criteria, 1357 pupils constituted the final working sample. The prevalence of dyslexia in the enrolled population ranged from 3.1% (95% CI 2.2-4.1%) to 3.2% (95% CI 2.4-4.3%) depending on different criteria adopted. In two out of three children with dyslexia the disorder had not been previously diagnosed. CONCLUSIONS: This study shows that dyslexia is largely underestimated in Italy and underlines the need for reliable information on prevalence, in order to better allocate resources both to Health Services and Schools