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Background: The prospective, single-arm, observational, phase 4 ETNA-AF Europe study collected real-world data about safety, effectiveness and therapeutic adherence in European patients with non-valvular atrial fibrillation newly prescribed with edoxaban and followed up for 4 years., Methods: Overall, 13 164 patients were included in the full-analysis set, which means that they had at least one documentation after baseline at 4 years. The current paper reports about the 3329 Italian patients out of the whole European population., Results: In the Italian cohort, median age was 76.0 (69.0-82.0) years, with 57.4% of the patients being ≥75 years old. The CHA2DS2-VASc score was >4 in 586 (18.1%) patients. At baseline, 670 (20.8%) patients were classified as frail by the investigators. Edoxaban 30 mg/day was prescribed to 1013 (31.8%) patients: these were older, with more comorbidities and a lower estimated creatinine clearance compared with those receiving 60 mg/day. All-cause mortality was 4.1%/year and there were very low yearly rates of bleeding and thromboembolic events: major bleeding, 0.9%; intracranial hemorrhage, 0.2%; ischemic stroke, 0.3%; systemic embolism, <0.1%. These events were more frequent in patients ≥75 years or in patients with renal impairment or treated with edoxaban 30 mg/day. Advancing age was not associated with an increased incidence of intracranial bleeding., Conclusions: These findings confirm the favorable long-term safety and effectiveness profile of edoxaban in non-valvular atrial fibrillation patients treated in routine clinical care in Italy.

Background: Tenosynovial Giant-Cell Tumour (TGCT) is a benign clonal neoplastic proliferation arising from the synovium, causing a variety of symptoms and often requiring repetitive surgery. This study aims to define the economic burden-from a societal perspective-associated with TGCT patients and their health-related quality of life (HRQOL) in six European countries., Methods: This article analyses data from a multinational, multicentre, prospective observational registry, the TGCT Observational Platform Project (TOPP), involving hospitals and tertiary sarcoma centres from six European countries (Austria, France, Germany, Italy, the Netherlands, and Spain). It includes information on TGCT patients' health-related quality of life and healthcare and non-healthcare resources used at baseline (the 12-month period prior to the patients entering the registry) and after 12 months of follow-up., Results: 146 TGCT patients enrolled for the study, of which 137 fulfilled the inclusion criteria. Their mean age was 44.5 years, and 62% were female. The annual average total costs associated with TGCT were €4866 at baseline and €5160 at the 12-month follow-up visit. The annual average healthcare costs associated with TGCT were €4620 at baseline, of which 67% and 18% corresponded to surgery and medical visits, respectively. At the 12-month follow-up, the mean healthcare costs amounted to €5094, with surgery representing 70% of total costs. Loss of productivity represented, on average, 5% of the total cost at baseline and 1.3% at follow-up. The most-affected HRQOL dimensions, measured with the EQ-5D-5L instrument, were pain or discomfort, mobility, and the performance of usual activities, both at baseline and at the follow-up visit. Regarding HRQOL, patients declared a mean index score of 0.75 at baseline and 0.76 at the 12-month follow-up., Conclusion: The results suggest that TGCT places a heavy burden on its sufferers, which increases after one year of follow-up, mainly due to the healthcare resources required-in particular, surgical procedures. As a result, this condition has a high economic impact on healthcare budgets, while the HRQOL of TGCT patients substantially deteriorates over time.

Background: HER2 amplification has been identified in 2-3% of patients with colorectal cancer, although there are currently no approved HER2-targeted therapies for colorectal cancer. We aimed to study the antitumour activity and safety of trastuzumab deruxtecan (an antibody-drug conjugate of humanised anti-HER2 antibody with topoisomerase I inhibitor payloads) in patients with HER2-expressing metastatic colorectal cancer., Methods: DESTINY-CRC01 is an open-label, phase 2 study that recruited patients from 25 clinics and hospitals in Italy, Japan, Spain, the UK, and the USA. Eligible patients had centrally confirmed HER2-expressing metastatic colorectal cancer that had progressed on two or more previous regimens (HER2-targeted therapies other than trastuzumab deruxtecan permitted), were aged 18 years or older (≥20 years in Japan), had an Eastern Cooperative Oncology Group score of 0 or 1, and had RAS and BRAF V600E wild-type tumours. Patients were enrolled into one of three cohorts by HER2 expression level: cohort A (HER2-positive, immunohistochemistry [IHC] 3+ or IHC2+ and in-situ hybridisation [ISH]-positive), cohort B (IHC2+ and ISH-negative), or cohort C (IHC1+). Patients received 6·4 mg/kg trastuzumab deruxtecan intravenously every 3 weeks until disease progression, unacceptable adverse events, withdrawal of consent, or death. The primary endpoint was confirmed objective response rate in cohort A by independent central review which was assessed in the full analysis set and safety was assessed in the safety analysis set. Both the full analysis set and the safety analysis set included all patients who received one or more doses of trastuzumab deruxtecan. This ongoing trial is registered with ClinicalTrials.gov, number NCT03384940., Findings: Between Feb 23, 2018, and July 3, 2019, 78 patients were enrolled in the study (53 in cohort A, seven in cohort B, and 18 in cohort C), all of whom received at least one dose of study drug. For the 53 (68%) patients with HER2-positive tumours (cohort A), a confirmed objective response was reported in 24 (45·3%, 95% CI 31·6-59·6) patients after a median follow-up of 27·1 weeks (IQR 19·3-40·1). Grade 3 or worse treatment-emergent adverse events that occurred in at least 10% of all participants were decreased neutrophil count (17 [22%] of 78) and anaemia (11 [14%]). Five patients (6%) had adjudicated interstitial lung disease or pneumonitis (two grade 2; one grade 3; two grade 5, the only treatment-related deaths)., Interpretation: Trastuzumab deruxtecan showed promising and durable activity in HER2-positive metastatic colorectal cancer refractory to standard treatment, with a safety profile consistent with that reported in previous trastuzumab deruxtecan trials. Interstitial lung disease and pneumonitis are important risks requiring careful monitoring and prompt intervention., Funding: Daiichi Sankyo., Competing Interests: Declaration of interests SS reports personal fees from and is an advisory board member for Daiichi-Sankyo, Amgen, Bayer, Bristol Myers Squibb, CheckmAb, Merck, Roche-Genentech, and Seattle Genetics. KR is an advisor and speaker for Bayer and Daiichi Sankyo, and an advisor for AstraZeneca, outside of the submitted work. MDB reports grants from Eli Lilly Italia and personal fees from Eli Lilly Italia and Bristol Myers Squibb outside the submitted work and is a consultant for Myland Italy and speaker for Bristol Myers Squibb, Merck, Sharp & Dohme, and Eli Lilly Italia. TM reports personal fees from Takeda, Chugai, Merck, Taiho, Bayer, Lilly Japan, Yakult Honsha, and Sanofi, and grants from MSD, Daiichi Sankyo, and Ono, outside the submitted work. HK reports non-financial support from Daiichi Sankyo, during the conduct of the study; grants, personal fees, and support for advisory role and honoraria (speeches) from Taiho, personal fees and support for advisory role and honoraria (speeches) from Bristol Myers Squibb Japan, Ono, and Lilly Japan, grants, personal fees, and upport for advisory role and honoraria (speeches) from Daiichi Sankyo, grants and personal fees from Chugai/Roche, personal fees from Yakult Pharmaceutical, Takeda, MSD KK, Merck Serono, Bayer, and AstraZeneca, and grants from Eisai, outside the submitted work. KY reports a grant from Daiichi Sankyo during the conduct of the study, and grants from Taiho, Sanofi, Ono, and Yakurt Honsha, and is a speaker for Taiho, Eli Lilly, Takeda, Chugai, Ono, Bristol Myers Squibb, Bayer, and Merck, outside the submitted work. TN reports a grant from Daiichi Sankyo during the conduct of the study, and grants from Taiho, Chugai, MSD, Ono, Bristol Myers Squibb, Lilly, and Dainippon Sumitomo. MF reports personal fees from Amgen, Array, Bayer, Guardant360, and Pfizer, and grants from Amgen, AstraZeneca, and Novartis, outside the submitted work. EE reports grants and personal fees from Hoffman-La Roche, Amgen, Merck Serono, and Servier, personal fees from Sanofi Aventis, and Array, honoraria institution support from MSD, and grants from Bristol Myers Squibb, during the conduct of the study. FC has served as an advisor and speaker for Roche, Amgen, Merck-Serono, Pfizer, Sanofi, Bayer, Servier, Bristol Myers Squibb, Celgene, and Eli Lilly, and received institutional research grants from Bayer, Roche, Merck-Serono, Amgen, AstraZeneca, and Takeda. YK reports grants from Daiichi Sankyo, during the conduct of the study, grants from A2 Healthcare, Dainippon Sumitomo, Eisai, EP – CRSU, EPS, Linical, NanoCarrier, QuintilesIMS, Sysmex, Astellas, Incyte, IQVIA, and Syneos Health Clinical KK, grants and personal fees from Bayer Yakuhin, Daiichi Sankyo, Lilly Japan, Linical, MSD KK, Taiho, Kyowa Kirin, Ono, Sanofi-Aventis, and Yakult Honsha, and personal fees from Bristol Myers Squibb, Chugai, EA Pharma, Takeda, Merck, Nipro, Pfizer Japan, Sawai, Shiseido, Asahi Kasei, Mitsubishi Tanabe, Merck, Shire Japan, Nippon Kayaku, Otsuka, and Novartis, outside the submitted work. TE reports grants and personal fees from MSD, Ono, Daiichi Sankyo, Bayer, Taiho, Lilly, Merck Serono, Nihon Kayaku, Bristol Myers Squibb, Eisai, Shionogi, Chugai, and Takeda, grants from Novartis, Dainippon Sumitomo, Astellas, Amgen, BeiGene, Array, Shionogi, and Yakult, and personal fees from Sanofi, outside the submitted work. ZW reports grants from Plexxikon and Novartis outside the submitted work, and is a consultant for Array, AstraZeneca, Bristol Myers Squibb, Bayer, Daiichi Sankyo, Novartis, Ono, Eli Lilly, Ipsen, Incyte, Merck, and EMD Serono. AS-B reports personal fees from Amgen, Bayer, Sanofi, and Servier, outside the submitted work. KS, EY, EB, YO, and JS are full-time employees of Daiichi Sankyo. AG reports grants from Daiichi Sanyko, during the conduct of the study, grants, personal fees, and non-financial support from Bayer, Merck, and Array/ Pfizer, and grants from OBI, outside the submitted work. TY reports grants from Novartis, MSD, Sumitomo Dainippon, Chugai, Sanofi, Daiichi Sankyo, Parexel, Ono, and GlaxoSmithKline, outside the submitted work. FL, JR, and KC declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: So far, the only available data for edoxaban periprocedural management come from the ENGAGE AF-TIMI 48 trial. The recently published EMIT-AF/VTE study showed low periprocedural bleeding and thromboembolic risks of edoxaban in a real-world setting in patients undergoing any diagnostic or therapeutic procedures. The aim of this study was to compare descriptively Italian and European data with regard to patient characteristics and outcomes in the EMIT-AF/VTE study., Methods: A total of 1155 patients treated with edoxaban for stroke prevention in non-valvular atrial fibrillation and with venous thromboembolism, and undergoing a wide range of diagnostic and therapeutic procedures were enrolled in 326 centers across Europe. Of these patients, 246 were from 43 Italian centers. The periprocedural interruption of edoxaban was at the physician's discretion. All the procedures were classified into minor, low, and high bleeding procedural risk according to the European Heart Rhythm Association (EHRA) definition. The primary outcome was the incidence of major bleeding. Secondary outcomes included thromboembolic events., Results: Patients were older in Italy in comparison with the rest of Europe with a mean age of 74.2 vs 71.3 years. Also, the rate of comorbidities was higher in Italy (e.g. diagnosed cancer and vascular disease) than in Europe. In Italy, there was a higher rate of high bleeding risk procedures than in other European countries (37.8% vs 20.6%) and a more homogeneous distribution of all types of procedures (while in Europe 44.1% were vascular access and transcatheter diagnostic procedures and interventions). In Italy, a higher proportion of patients did not interrupt edoxaban (32.9% vs 29% in Europe). The number of major bleeding events (2 in Italy, 3 in Europe) as well as of thromboembolic events (4 in Italy, 3 in Europe) was overall low., Conclusions: In the EMIT-AF/VTE study, the number of bleeding and thromboembolic events in patients treated with edoxaban undergoing elective or unplanned procedures was low either in Italy or in the rest of Europe. The safety and efficacy of edoxaban was confirmed in Italy even if patients were older, presented more frequently with cancer, and there was a higher rate of high bleeding risk procedures by EHRA definition.

Introduction: The Coronavirus disease 2019 (COVID-19) outbreak is a whole Earth health emergency related to a highly pathogenic human coronavirus responsible for severe acute respiratory syndrome (SARS-CoV-2). Despite the fact that the majority of infected patients were managed in outpatient settings, little is known about the clinical characteristics of COVID-19 patients not requiring hospitalization. The aim of our study was to describe the clinical comorbidity and the pharmacological therapies of COVID-19 patients managed in outpatient settings., Materials and Methods: We performed an observational, retrospective analysis of laboratory-confirmed COVID-19 patients managed in outpatient settings in Naples, Italy between 9 March and 1 May 2020. Data were sourced from the prospectively maintained Health Search (HS)/Thales database, shared by 128 primary care physicians (PCPs) in Naples, Italy. The clinical features and pharmacological therapies of COVID-19 patients not requiring hospitalization and managed in outpatient settings have been described., Results: A total of 351 laboratory-confirmed COVID-19 patients (mean age 54 ± 17 years; 193 males) with outpatient management were evaluated. Hypertension was the most prevalent comorbidity (35%). The distribution of cardiovascular comorbidities showed no gender-related differences. A total of 201 patients (57.3%) were treated with at least one experimental drug for COVID-19. Azithromycin, alone (42.78%) or in combination (27.44%), was the most widely used experimental anti-COVID drug in outpatient settings. Low Molecular Weight Heparin and Cortisone were prescribed in 24.87% and 19.4% of the study population, respectively. At multivariate regression model, diabetes (risk ratio (RR): 3.74; 95% CI 1.05 to 13.34; p = 0.04) and hypertension (RR: 1.69; 95% CI 1.05 to 2.7; p = 0.03) were significantly associated with the experimental anti-COVID drug administration. Moreover, only diabetes (RR: 2.43; 95% CI 1.01 to 5.8; p = 0.03) was significantly associated with heparin administration., Conclusions: Our data show a high prevalence of hypertension, more likely treated with renin-angiotensin-aldosterone system (RASS) inhibitors, among COVID-19 patients not requiring hospitalization. Experimental COVID-19 therapies have been prescribed to COVID-19 patients considered at risk for increased venous thromboembolism based on concomitant comorbidities, in particular diabetes and hypertension.