[Clinical trials approved by Aifa for Covid-19: report of the main results to fill the unmet medical need.] / Le sperimentazioni cliniche approvate dall'Aifa per Covid-19: report dei risultati principali per colmare l'unmet medical need.

INTRODUCTION: the rapidity with which the Coronavirus epidemic emergency exploded took the scientific community by surprise, unprepared for such an event. The objective of this work is to evaluate, to date, the state of the art of the clinical trials approved by Aifa, analyzing the characteristics of the single completed and published trials and the authorization status for the use of the drugs under study in the treatment of Covid-19. MATERIALS AND METHODS: The protocols available for each clinical study were extrapolated from the Aifa website relating to the management of clinical trials in Italy during the Covid-19 emergency; the unique EudraCT and Nct codes were extrapolated from these, verifying their publication using the PubMed search engine, the ClinicalTrials.gov platform, the EU Clinical Trials Register portal and the website of the pharmaceutical company identified as the promoter of the study. The characteristics of the individual trials useful for the analysis were extracted from the published papers. Finally, a comparison was made between the studies relating to experimental drugs which were subsequently authorized for the Covid-19 indication and the studies relating to drugs which have not yet been authorized to date. RESULTS: In total, Aifa approved 94 between March 2020 and March 2022; of these, 22 are not listed on ClinicalTrials.gov; of the 72 trials listed on ClinicalTrials.gov, 31 (43%) were published, for a total of 25 drugs. Of the authorized and published trials, 26 report the "mortality endpoint". The most studied drugs are remdesivir and tocilizumab with 3 studies each, methylprednisone and molnupravir with 2. 14 studies are phase III, of these 12 used a drug as an experimental treatment which was then approved for Covid-19. Of the 41 trials present on ClinicalTrials.gov that have not yet been published, 21 are terminated. The drugs anakinra, remdesivir, molnupravir, regdanvimab, tocilizumab, AZD1222 vaccine have been updated/registered for Covid-19 indication; anakinra, baricitinib, tocilizumab and sarilumab have been included in the list of Law 648/96; remdesivir, canakinumab and ruxolitinib have been entered into compassionate use programmes. DISCUSSION AND CONCLUSIONS: The methods of early access to therapy have allowed an alternative to patients who are not eligible for the ongoing trials. The challenge that the scientific community has faced has strengthened the culture of evidence-based medicine.

Emilia-Romagna Regional Blood System accreditation as an example of improvement through application of specific requirements: a retrospective analysis.

BACKGROUND: Institutional accreditation in Italy represents the license given by a region to a public or private facility to provide services in the name and on behalf of the National Health Service. This study aims to evaluate the improvement of the Emilia-Romagna Regional Blood System and to highlight its unresolved issues, analysing non-conformities observed during accreditation and maintenance inspections between 2013 and 2018. METHODS: All the Emilia-Romagna Regional Blood facilities were invited to participate in this study voluntarily and anonymously. Participants had to access a web application that we developed specifically. For each of the three inspections evaluated in this study, they had to enter data about the state of their organisation branches and non-conformities observed by regional inspectors. All data entered were finally exported from the web application database and analysed with spreadsheets. Statistical analysis was performed using Wilcoxon signed-rank test with continuity correction. RESULTS: 17 structures took part in the study, with a total of 174 organisation branches. The number of branches changed over the years because of new openings and closures due to reorganisations or non-conformities that were too difficult to correct. Inspectors observed 2381 non-conformities (291 structural, 611 technological and 1479 organisational). As a result of accreditation inspections and consequent improvement actions, non-conformities were reduced by 88%. The most frequent non-conformities concerned the management software and the transportation of blood and blood components. CONCLUSION: An improvement in the Emilia-Romagna Regional Blood System over time is evident: institutional accreditation certainly pushed it to change and overcome its problems to comply with specific requirements. The remaining non-conformities after the three inspections were mostly organisational and management software was the most critical issue. Despite these non-conformities, all currently active structures are accredited and guarantee high standards of quality and safety of products and services.

COVID-19 Outbreak in Italy: Report on the First 124 Consecutive Patients Treated at Home.

North Italy emerged as an epicenter of COVID-19 in the Western world. The majority of studies of patients with COVID-19 have focused on hospitalized patients, and data on early outpatient treatment are limited. This research retrospectively examines consecutive symptomatic adults who did not present to a hospital but who experience laboratory confirmed (nasopharyngeal swabs) or probable COVID-19 infection. From March 12 to April 12, 2020, 124 consecutive patients with laboratory-confirmed COVID-19 infection (84%) or with epidemiologically linked exposure to a person with confirmed infection (16%) were managed at home. The diagnosis of pneumonia was made with a portable ultrasound. COVID-19 treatment was based on low-dose hydroxychloroquine with or without darunavir/cobicistat or azithromycin and enoxaparine for bedridden patients. The patients were monitored by telemedicine. The primary endpoints were clinical improvement or hospitalization, and the secondary endpoints were mortality at day 30 and at day 60. Forty-seven (37.9%) patients had mild COVID-19 infection, 44 (35.5%) had moderate COVID-19 infection, and 33 (26.6%) had severe COVID-19 infection. Four patients (3.2%) were hospitalized and there were no deaths at day 30 and at day 60. Only mild side effects were reported. Early home treatment of COVID-19 patients resulted in a low hospitalization rate with no deaths, with the limitations of the small sample size and that it was conducted within a single geographic area. We believe that this model may be easily reproduced in both cities and rural areas around the world to treat COVID-19 infection.

Cancer patients with COVID-19: a retrospective study of 51 patients in the district of Piacenza, Northern Italy.

BACKGROUND: Cancer patients are considered a highly fragile group in the current coronavirus disease 2019 (COVID-19) pandemic. MATERIAL & METHODS: In this study, patients with COVID-19 and cancer, hospitalized in Piacenza, Italy, from 4 April to 4 May 2020 were included. Risk factors for death were analyzed. RESULTS: Fifty-one COVID-19 cancer patients were included, of which the median age was 71.02 years (range: 51-86) and 70.59% were male. Cancer types included gastrointestinal (25.49%), genitourinary (25.49%) and lung (23.53%). Forty-five (88.24%) patients received hydroxychloroquine-based therapy. In addition, 25 of 51 patients died (49%): 12 of 51 (23.53%) owing to cancer and 13 of 51 (25.49%) owing to COVID-19. CONCLUSION: The risks for death were related to later onset of treatment for COVID-19, severe/critical COVID-19, age, elevated basal CRP and elevated lactate dehydrogenase.

Insulin-like growth factor 1 as a predictor of ischemic stroke outcome in the elderly.

PURPOSE: To examine whether serum insulin-like growth factor 1 (IGF-1) and IGF binding protein 3 (IGFBP-3) concentrations, determined early after the onset of stroke, are predictive of clinical outcome in elderly patients. METHODS: The sample comprised 85 patients (mean [+/- SD] age, 83 +/- 7.4 years; range, 67 to 99 years; 34% male) who were admitted with acute stroke to a geriatric ward between January 1998 and June 2000, and 88 control patients who were similar in age and sex. Clinical and laboratory assessments, computed tomographic scan of the head, carotid ultrasonography, and electrocardiography were employed to define the clinical and etiologic stroke subtype. Fasting blood samples were collected within 24 hours of admission for IGF-I and IGFBP-3 measurement. Univariate and multiple logistic regression analyses, with adjustment for other related clinical covariates, were used to assess the relation of IGF-I and IGFBP-3 to poor outcome, defined as severe disability (Barthel index <60/100) or death, at 1 month (or at discharge), 3 months, and 6 months. RESULTS: Mean (+/- SD) IGF-1 levels were lower in patients with stroke than in controls (69 +/- 45 ng/mL vs. 102 +/- 67 ng/mL, P adjusted for age = 0.001). The mean IGF-1/IGFBP-3 molar ratio was also lower in stroke patients (0.12 +/- 0.07 vs. 0.19 +/- 0.09, P adjusted for age <0.0001). However, there was no relation of hormone levels to either the clinical subtype of stroke or the extent of neurologic impairment. IGF-1 levels were inversely related to poor outcome (mainly death) at 3 and 6 months, independent of other clinical covariates that were highly predictive of outcome, such as age and stroke scale score on admission (hazard ratio for death at 6 months for each 20-ng/mL increase = 0.7; 95% confidence interval: 0.5 to 0.9). An independent association of the molar ratio with death at 3 and 6 months was also found. CONCLUSION: Low levels of circulating IGF-1 may predict the clinical outcome of stroke in elderly patients.