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Background: the long-COVID condition is gaining increasing relevance in terms of public health, but few studies have evaluated its impact on use of healthcare resources and the organizational responses of healthcare systems. Although many studies have evaluated case studies of individuals with long-COVID, the clinical spectrum of symptoms is still poorly defined due to the heterogeneity of the populations studied, the variability of the definitions used, and the absence of disease markers. In this context, in 2022, a project was designed and implemented in cooperation between the National Centre for Prevention and Control of the Italian Ministry of Health and the Italian National Health Institute (Istituto Superiore di Sanità, ISS)., Objectives and Methods: this project was articulated into five main objectives: 1. definition of the health care dimensions of the long-COVID phenomenon. This objective included an analysis of regional data flows to measure use of hospitalization services (acute, rehabilitation, long-term care), resource consumption (specialist visits and drug consumption), and the rate of institutionalization in patients with a history of COVID-19; 2. definition of number, characteristics, and distribution of long-COVID centres across the national territory. This objective has been implemented through a national survey of long-COVID diagnosis and assistance centres; 3. definition of clinical good practices about the management of long-COVID condition by a multidisciplinary group of experts; 4. definition of a long-COVID surveillance system; including the definition of a specific data set of information and the identification of a sample of clinical centres that deal with the care of subjects with long-term effects of COVID-19 and the setup of a dedicated online platform; a phone survey based on more than 1,000 interviews assessed the spectrum of symptoms reported; 5. structuring a national network and providing information, which included networking of the centres participating in the study with the dissemination of periodic information and update workshops or webinars; the creation of a website dedicated to the long-COVID condition, with general information for citizens and a section dedicated to the project; training activities., Results: Objective 1: a cohort study of over 600,000 individuals showed that people exposed to SARS-CoV-2 infection, particularly those who were hospitalized, appear to use more healthcare resources in the 6 months following infection than those who were not exposed. Individuals hospitalized in intensive care showed rates of outpatient visits 3 times higher than those who were not exposed and over 4 times higher rates for diagnostic imaging tests and hospitalizations. The case-control study found an increased risk of initiating antidepressant therapy among individuals exposed to SARS-CoV-2 infection compared to those who were not exposed, particularly among those who were hospitalized during acute infection. Furthermore, COVID-19 vaccination may play a protective role in this context. Objective 2: 124 clinical centres completed the questionnaire developed to define the patterns of clinical care for patients with long-COVID. Most centres provided care through outpatient visits or day hospital services with scheduled visits or referral to primary care and had specialist skills that allowed a multidisciplinary approach to the subject with suspected long-COVID condition. Objective 3: a multidisciplinary team, representative of the multi-systemic nature of long-COVID, with the participation of 16 experts, developed recommendations for the management of patients with long-COVID, based on current knowledge on the topic, with the aim of contributing to standardizing the activities of clinical centres throughout Italy. Objective 4: the clinical surveillance system has allowed the collection of data from over 1,200 patients from 30 clinical centres for the definition of symptom, their aggregation in clusters, and associated factors. Information on symptom profile was also assessed through a phone survey of more than 1,000 participants. Objective 5: the ISS website on long COVID provided information on the long-COVID condition and illustrated the CCM project, with links to webinars and workshops. In addition, a FAD course - entitled 'long-COVID: a new clinical scenario' - was implemented on the EDU-ISS platform, with over 14,000 participants., Conclusions: the results of this study show that long-COVID is a frequent condition in our country, which, due to the amplitude of numbers and the spectrum of symptoms, has a substantial impact on resource consumption. This demonstrates that it will be necessary to implement, guarantee and monitor well-defined care standards for this condition.

The human normal intestinal flora prevents the colonization of exogenous bacteria, maintaining a constant microecology: this property is called "colonization resistance". In leukemia patients antibiotics used for prevention and/or therapy of infectious episodes can alter the intestinal microecology, so that the gut can represent the trigger zone for generalized septicemia. Moreover cytotoxic drugs used in these patients can favour intestinal disturbances. In our study we evaluated the in vitro activity of three commonly used antineoplastic drugs (Daunorubicin, Cytosine arabinoside, Methotrexate) against aerobic and anaerobic intestinal bacteria and Clostridium difficile that is the aetiological agent of pseudomembranous colitis. Daunorubicin proved to be the most active inhibiting, in concentration ranging from 16 to 128 micrograms/ml, 50% of Bacteroides strains and 90% of Clostridium difficile and Enterococci strains tested. Methotrexate showed activity only against some Bacteroides strains, while Cytosine arabinoside had no activity at all. We conclude that in these patients the use of these drugs may represent another factor of risk altering the intestinal flora and so lowering the colonization resistance.

Intestinal microflora changes in ten adult and healthy subjects after storage of specimen with different modalities, temperatures and times were evaluated quantitatively and qualitatively. Aerobic components (Enterobacteriaceae, Enterococcus, Staphylococcus and Bacillus spp.) did not show considerable variations of concentration in all maintenance conditions. Anaerobic components showed different capacity of survival for every researched genus: Clostridia and Lactobacilli, even kept frozen for one month in glycerol broth at -70 degrees C, maintained a stable viable count; Bacteroides, Fusobacteria, Veillonellae and Peptostreptococci were found stable after one week, while after one month showed a loss of concentration superior to 4 Log; Eubacteria were found remarkably reduced after seven days and completely lost after one month.