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Introduction: The Istituto Superiore di Sanita and the Agenzia Italiana del Farmaco coordinate the project TheShinISS-Vax, Flu, a post-marketing "active" surveillance of influenza vaccines. We report the results of the investigation using the Self- Controlled Case Series (SCCS) design on influenza vaccine and Guillain-Barre syndrome in vaccinated population aged over than 6 months, during the influenza vaccine campaign 2020-2021 in Italy. Materials and methods: A SCCS multi-regional study was carried out using linked data from Regional Health Care Registries of Valle d'Aosta, Friuli Venezia Giulia, Emilia-Romagna, Toscana, Lazio, Campania, and Puglia. Relative incidence of Guillain-Barre syndrome was estimated, comparing the exposure risk periods (0-41 days from the vaccination day, subdivided in six intervals) with the unexposed period.
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Background: Pulse glucocorticoid therapy (> 250 mg of prednisone equivalent per day for 1 or a few days) is used in many immuno-inflammatory diseases for its quick and strong anti-inflammatory effect in emergency situations. It was used during in Severe Acute Respiratory Syndrome epidemics with no consistent data regarding its benefits. The efficacy and safety of this therapy associated to dexamethasone in coronavirus disease 2019 (Covid-19) pneumonia are unclear. Methods: We conducted a double-blind, randomized, placebo-controlled trial in hospitalized patients with COVID19-pneumonia. The study population included patients hospitalized for recent-onset Covid-19 pneumonia requiring supplemental oxygen in any delivery mode, except invasive mechanical ventilation, with PaO2/FiO2 between 100 and 300, and a C-reactive protein greater than 5 mg/dl. Patients were randomly assigned to receive 1 gram of methylprednisolone for 3 consecutive days or placebo in addition to standard dexamethasone. The primary outcome was the duration of the patient hospitalization, calculated as the time interval between randomization and hospital discharge without the need of supplementary oxygen. All-cause mortality, survival free from invasive ventilation and safety were also evaluated. Written informed consent was obtained from each patient or from the patient's legally authorized representative if the patient was unable to provide consent. Results: A total of 304 patients underwent randomization in 19 Italian sites between December 21, 2020, and March 10, 2021. Three patients retired the consent to the study one day after randomization, leaving 301 patients eligible for intention to treat analyses. 112 of 151 (74.2%) patients in the pulse methylprednisolone arm and 111 of 150 (74.0%) patients in the placebo arm were discharged from hospital without oxygen (p = 0.528) within 28 days from randomization. We did not observe any significant differences between pulse methylprednisolone and placebo arms in terms of admission to Intensive Care Unit with orotracheal intubation or death (19.9% versus 16.0% respectively;hazard ratio, 1.27;95%CI, 0.74-2.16), or in terms of overall mortality (9.3% versus 11.3% respectively;hazard ratio, 0.82;95%CI, 0.40-1.66). Serious adverse events occurred in 9 patients (6.0%) in the methylprednisolone pulse group and in 12 patients (8.0%) in the placebo group. Conclusion: Methylprednisolone pulse therapy in addition to dexamethasone was not of benefit in patients with COVID-19 pneumonia.
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Background: Muscle and fat mass loss as a consequence of protein catabolism and prolonged immobilization is frequent in critically ill patients. Post-COVID acute sarcopenia may be due also to inflammaging for the strong inflammatory reaction. The study aims were to describe changes in chest CT body composition parameters from baseline to follow-up CT scan in severe COVID-19 survivors, and to evaluate the impact of COVID-19 inflammatory burden on these changes. Methods: Baseline (t0), 2-3 months (t1) and 6-7 months (t2) follow-up CT scan of severe COVID-19 pneumonia survivors were retrospectively reviewed to measure pectoralis muscle area (PMA) and density (PMD), liver-to-spleen ratio (LSR), and total, visceral, and intermuscular adipose tissue areas (TAT, VAT and IMAT) at T7-T8 vertebrae. C-reactive protein (CRP) curve integral was used to describe COVID-19 inflammatory burden, and its impact on body composition changes was evaluated in multivariable linear regression models adjusted for age, sex, and baseline TAT (index of general adiposity). Results: At follow-up a decrease in mean PMA and in all mean body fat areas was registered, faster from t0 to t1, and slower from t1 to t2, with the exception of PMD, which increased (i.e. intramuscular fat decreased) only from t1 to t2 (Table). Mean VAT decrease was more conspicuous than mean TAT decrease. In models adjusted for age, sex, and baseline TAT, increasing CRP integral was significantly associated with higher PMA reduction (p=0,017 for delta t2-t0) and lower PMD increase (p=0.01 for delta t2-t0), higher LSR increase (i.e. higher steatosis decrease) (p<0.0001 for delta t1-t0, n.s. for delta t2-t0), and higher VAT decrease (p=0.035 for delta t2-t0), but not with TAT decrease. These associations were stronger in patients with higher VAT and lower LSR at baseline. Conclusion: Muscle and fat loss after COVID-19 is faster in the first months, but slowly continues till 6-7 months. Fat loss is more apparent in visceral compartments. Inflammatory burden is associated with the degree of muscle and visceral/liver fat loss.
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Objective: Chloroquine (CLQ)/hydroxychloroquine (HCQ) are two of the most studied drugs for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. There are very limited data on the effect of treatment of patients affected by rheumatic diseases with HCQ/CLQ and other conventional disease-modifying anti-rheumatic drugs (cDMARDs) on COVID-19. The aim of this study is to investigate the hypothesis that treatment of rheumatic diseases with hydroxychloroquine (HCQ)/chloroquine (CLQ) as compared to other conventional disease-modifying anti-rheumatic drugs (cDMARDs) might decrease the COVID-19-related risk of hospitalization and mortality. Methods: This large-scale case-control study nested within a cohort of cDMARD users was conducted in the Lombardy, Veneto, Tuscany and Lazio regions and Reggio Emilia (Emilia Romagna) Local Health Unit, covering a total of 25.1 million inhabitants. Claims databases were linked to loco-regional COVID-19 surveillance registries from the same catchment area through unique fully-anonymized patient identifiers. Risk of COVID-19-related outcomes was estimated as odds ratios (ORs) along with 95% confidence intervals (CIs), using a multivariate conditional logistic regression analysis, by comparing HCQ/CLQ vs methotrexate (primary comparator) and other cDMARDs (secondary comparator). In addition, the same risk for HCQ/CLQ, methotrexate and other cDMARDs separately vs nonuse of these drugs as well as for presence of rheumatic diseases vs. absence in a non-nested population was investigated. Results: From the cohort of cDMARD users, 1275 cases who were hospitalized due to COVID-19 were identified and matched to 12,734 controls. When compared to recent use of methotrexate, no statistically significant association between recent HCQ/CLQ monotherapy with COVID-19 hospitalization (OR 0.83 [95% CI, 0.69 to 1.00]) or mortality (OR 1.19 [95% CI, 0.85 to 1.67]) was observed. A statistically significant lower risk was found when comparing recent use of HCQ/CLQ to treatment with other cDMARDs and glucocorticoids concomitantly. In the sensitivity analysis in the non-nested population, HCQ/CLQ was not associated with COVID-19 hospitalization as compared with non-use, whereas a mild statistically significant increased risk for recent use of both methotrexate as monotherapy (OR 1.19 [95% CI, 1.05 to 1.34]) or other cDMARDs (OR 1.21 [95% CI, 1.08 to 1.36]) vs non-use was found. Finally, the presence of rheumatoid arthritis or systemic lupus erythematosus was not associated with COVID-19 hospitalization (OR 0.98 [95% CI, 0.89 to 1.07]) or mortality (OR 0.88 [95% CI, 0.74 to 1.05]). Conclusion: Prior exposure to HCQ/CLQ in rheumatic patients was not associated with a protective effect against COVID-19-related hospitalization and mortality. On the contrary, an increased risk in patients receiving other cDMARDs was observed when compared to non-use, especially in those patients concomitantly treated with glucocorticoids. This is likely attributable to a synergistic immunosuppressive effect, leading to increased risk of severe SARS-CoV-2 infection.
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Background and aims: Many clinical trials on potentially disease-modifying drugs are focused to mild cognitive impairment (MCI) prodromal-to-Alzheimer's disease. The MCI population actually includes patients with higher risk of progression to AD. Since the new drugs, if effective, will carry both elevated unit costs and not marginal side effects, they should be administered selectively to high-risk subjects. The Italian INTERCEPTOR project, promoted by the Italian Medicine Agency and the Italian Ministry of Health, is a multicenter, interventional, nontherapeutic cohort study in subjects with MCI, with the primary aim of identifying biomarkers that better predict the conversion to AD after 3 years of follow-up. Methods: A sample of 500 subjects with MCI was planned to be enrolled. The biomarkers under investigation obtained by the analysis of MMSE, CSF, FDG-PET, FCRST, APOE4, EEG, Volumetric MRI. Multivariate prediction model will provide the predictive performance of each biomarker and combinations. In applying biomarkers, three scenarios are considered: 1) use of cut-offs indicated by experts 2) defining new optimal cut-offs for the specific population 3) use of values in a continuous form in order to evaluate all predictive information. Finally, nomograms will be defined for use in clinical practice. Results: Due to COVID-19, the target sample size was not reached. The enrolment was closed on October 31st 2020. Overall 498 patients were screened, 362 recruited into the study and 17 dropped out. Conclusions: The findings will support the diagnostic path redefinition to identify those patients in the early stage eligible to prescription for disease-modifying medications.