Prolonged higher dose methylprednisolone vs. conventional dexamethasone in COVID-19 pneumonia: a randomised controlled trial (MEDEAS)

Background: Dysregulated systemic inflammation is the primary driver of mortality in severe coronavirus disease 2019 (COVID-19) pneumonia. Current guidelines favour a 7-10-day course of any glucocorticoid equivalent to dexamethasone 6 mg daily. A comparative randomised controlled trial (RCT) with a higher dose and a longer duration of intervention was lacking. Methods: We conducted a multicentre, open-label RCT to investigate methylprednisolone 80 mg as a continuous daily infusion for 8 days followed by slow tapering versus dexamethasone 6 mg once daily for up to 10 days in adult patients with COVID-19 pneumonia requiring oxygen or noninvasive respiratory support. The primary outcome was reduction in 28-day mortality. Secondary outcomes were mechanical ventilation-free days at 28 days, need for intensive care unit (ICU) referral, length of hospitalisation, need for tracheostomy, and changes in C-reactive protein (CRP) levels, arterial oxygen tension/inspiratory oxygen fraction (P aO2 /F IO2 ) ratio and World Health Organization Clinical Progression Scale at days 3, 7 and 14. Results: 677 randomised patients were included. Findings are reported as methylprednisolone (n=337) versus dexamethasone (n=340). By day 28, there were no significant differences in mortality (35 (10.4%) versus 41 (12.1%); p=0.49) nor in median mechanical ventilation-free days (median (interquartile range (IQR)) 23 (14) versus 24 (16) days; p=0.49). ICU referral was necessary in 41 (12.2%) versus 45 (13.2%) (p=0.68) and tracheostomy in 8 (2.4%) versus 9 (2.6%) (p=0.82). Survivors in the methylprednisolone group required a longer median (IQR) hospitalisation (15 (11) versus 14 (11) days; p=0.005) and experienced an improvement in CRP levels, but not in P aO2 /F IO2 ratio, at days 7 and 14. There were no differences in disease progression at the prespecified time-points. Conclusion: Prolonged, higher dose methylprednisolone did not reduce mortality at 28 days compared with conventional dexamethasone in COVID-19 pneumonia

Prolonged higher dose methylprednisolone vs. conventional dexamethasone in COVID-19 pneumonia: a randomised controlled trial (MEDEAS)

Dysregulated systemic inflammation is the primary driver of mortality in severe COVID-19 pneumonia. Current guidelines favor a 7-10-day course of any glucocorticoid equivalent to dexamethasone 6 mg·day-1. A comparative RCT with a higher dose and a longer duration of intervention was lacking

COVID-19 in rheumatic diseases in Italy: first results from the Italian registry of the Italian Society for Rheumatology (CONTROL-19)

OBJECTIVES: Italy was one of the first countries significantly affected by the coronavirus disease 2019 (COVID-19) epidemic. The Italian Society for Rheumatology promptly launched a retrospective and anonymised data collection to monitor COVID-19 in patients with rheumatic and musculoskeletal diseases (RMDs), the CONTROL-19 surveillance database, which is part of the COVID-19 Global Rheumatology Alliance. METHODS: CONTROL-19 includes patients with RMDs and proven severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) updated until May 3rd 2020. In this analysis, only molecular diagnoses were included. The data collection covered demographic data, medical history (general and RMD-related), treatments and COVID-19 related features, treatments, and outcome. In this paper, we report the first descriptive data from the CONTROL-19 registry. RESULTS: The population of the first 232 patients (36% males) consisted mainly of elderly patients (mean age 62.2 years), who used corticosteroids (51.7%), and suffered from multi-morbidity (median comorbidities 2). Rheumatoid arthritis was the most frequent disease (34.1%), followed by spondyloarthritis (26.3%), connective tissue disease (21.1%) and vasculitis (11.2%). Most cases had an active disease (69.4%). Clinical presentation of COVID-19 was typical, with systemic symptoms (fever and asthenia) and respiratory symptoms. The overall outcome was severe, with high frequencies of hospitalisation (69.8%), respiratory support oxygen (55.7%), non-invasive ventilation (20.9%) or mechanical ventilation (7.5%), and 19% of deaths. Male patients typically manifested a worse prognosis. Immunomodulatory treatments were not significantly associated with an increased risk of intensive care unit admission/mechanical ventilation/death. CONCLUSIONS: Although the report mainly includes the most severe cases, its temporal and spatial trend supports the validity of the national surveillance system. More complete data are being acquired in order to both test the hypothesis that RMD patients may have a different outcome from that of the general population and determine the safety of immunomodulatory treatments

Statin use and bleeding risk during vitamin K antagonist treatment for venous thromboembolism: A multicenter retrospective cohort study

12nononenoneRiva, Nicoletta; Di Minno, Matteo N.D.; Mumoli, Nicola; Pomero, Fulvio; Franchini, Massimo; Bellesini, Marta; Lupoli, Roberta; Sabatini, Silvia; Borretta, Valentina; Bonfanti, Carlo; Ageno, Walter; Dentali, FrancescoRiva, Nicoletta; Di Minno, Matteo N. D.; Mumoli, Nicola; Pomero, Fulvio; Franchini, Massimo; Bellesini, Marta; Lupoli, Roberta; Sabatini, Silvia; Borretta, Valentina; Bonfanti, Carlo; Ageno, Walter; Dentali, Francesc

Poor predictive value of contemporary bleeding risk scores during long-term treatment of venous thromboembolism: A multicentre retrospective cohort study

13nononeBleeding is a common and feared complication of oral anticoagulant therapy. Several prediction models have been recently developed, but there is a lack of evidence in patients with venous thromboembolism (VTE). The aim of this study was to validate currently available bleeding risk scores during long-term oral anticoagulation for VTE. We retrospectively included adult patients on vitamin K antagonists for VTE secondary prevention, followed by five Italian Anticoagulation Clinics (Cuneo, Livorno, Mantova, Napoli, Varese), between January 2010 and August 2012. All bleeding events were classified as major bleeding (MB) or clinically-relevant-non-major-bleeding (CRNMB). A total of 681 patients were included (median age 63 years; 52.0% female). During a mean follow-up of 8.82 (± 3.59) months, 50 bleeding events occurred (13 MB and 37 CRNMB), for an overall bleeding incidence of 9.99/100 patient-years. The rate of bleeding was higher in the first three months of treatment (15.86/100 patient-years) than afterwards (7.13/100 patient-years). The HAS-BLED showed the best predictive value for bleeding complications during the first three months of treatment (area under the curve [AUC] 0.68, 95% confidence interval [CI] 0.59–0.78), while only the ACCP score showed a modest predictive value after the initial three months (AUC 0.61, 95%CI 0.51–0.72). These two scores had also the highest sensitivity and the highest negative predictive value. None of the scores predicted MB better than chance. Currently available bleeding risk scores had only a modest predictive value for patients with VTE. Future studies should aim at the creation of a new prediction rule, in order to better define the risk of bleeding of VTE patients.Riva, Nicoletta; Bellesini, Marta; Di Minno, Matteo Nicola Dario; Mumoli, Nicola; Pomero, Fulvio; Franchini, Massimo; Fantoni, Chiara; Lupoli, Roberta; Brondi, Barbara; Borretta, Valentina; Bonfanti, Carlo; Ageno, Walter; Dentali, FrancescoRiva, Nicoletta; Bellesini, Marta; Di Minno, Matteo Nicola Dario; Mumoli, Nicola; Pomero, Fulvio; Franchini, Massimo; Fantoni, Chiara; Lupoli, Roberta; Brondi, Barbara; Borretta, Valentina; Bonfanti, Carlo; Ageno, Walter; Dentali, Francesc

Use of integrated real-time continuous glucose monitoring/insulin pump system in children and adolescents with type 1 diabetes: a 3-year follow-up study

Insulin pumps and real-time continuous glucose monitoring devices have recently been combined into the sensor-augmented pump (SAP) system. The objective of this study was the evaluation of the clinical use of SAP in a large series of children with type 1 diabetes using insulin pump therapy

Insulin pump therapy in children and adolescents with type 1 diabetes: the Italian viewpoint.

Background and Aim: A panel of experts of the Italian Society of Paediatric Endocrinology and Diabetology translated into Italian the international insulin pump therapy recommendations in children and adolescents with type 1 diabetes. Methods: After an extensive review of the literature using evidence-based recommendations, several issues were taken into account, such as patient selection, advantages and disadvantages, instrument choice, insulin type, therapy planning and follow-up, emergencies, nutrition, particular occasions (like parties, holidays, sick days, travels), exercise, continuous glucose monitoring and integrated system, neonatal diabetes. The panel evaluated the cost-effectiveness of insulin pump therapy compared to multiple daily injection therapy, analysing the cost-benefit ratio. Results: Some tweak was needed due to the Italian dietetic singularity, meal schedule, climate and lifestyle. Insulin pump therapy in neonatal diabetes is a new issue and no guidelines have been published yet for this age-group. Moreover, legal issues according to the Italian law have been added and are peculiarity of our recommendations. An "informed therapeutic agreement" between the patient and his/her family and the diabetic team has to be signed before starting insulin pump therapy. Conclusions: We think that nowadays the need for clinical guidelines is important and worth the effort that all countries develop faithful adaptation into their local languages taking into account specific contexts and local peculiarities, without making substantial modifications to the original text. © Mattioli 1885

Recurrent Thrombotic Events after Discontinuation of Vitamin K Antagonist Treatment for Splanchnic Vein Thrombosis: A Multicenter Retrospective Cohort Study

It is generally recommended that patients with splanchnic vein thrombosis (SVT) should receive a minimum of 3 months of anticoagulant treatment. However, little information is available on the long-term risk of recurrent thrombotic events. The aim of this study was to evaluate the risk of venous and arterial thrombosis after discontinuation of vitamin K antagonist (VKA) in SVT patients. Retrospective information from a cohort of SVT patients treated with VKA and followed by 37 Italian Anticoagulation Clinics, up to June 2013, was collected. Only patients who discontinued VKA and did not receive any other anticoagulant drug were enrolled in this study. Thrombotic events during follow-up were centrally adjudicated. Ninety patients were included: 33 unprovoked SVT, 27 SVT secondary to transient risk factors, and 30 with permanent risk factors. During a median follow-up of 1.6 years, 6 venous and 1 arterial thrombosis were documented, for an incidence of 3.3/100 patient-years (pt-y). The recurrence rate was highest in the first year after VKA discontinuation (8.2/100'pt-y) and in patients with permanent risk factors (10.2/100'pt-y). Liver cirrhosis significantly increased the risk of recurrence. In conclusion, the rate of recurrent vascular complications after SVT is not negligible, at least in some patient subgroups